HETEROCYCLIC DERIVATIVES AS SPHINGOSINE-1-PHOSPHATE 3 INHIBITORS FIELD OF THE INVENTION The present invention relates to heterocyclic derivatives their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them. More particularly the present invention relates to their use in inhibiting Sphingosine-1-Phosphate (S1P3) receptor mediated biological activity. BACKGROUND OF THE INVENTION Lysophospholipids (LPLs), like sphingosine-1-phosphate (S1P) are lipid signalling molecules that are derived from cell membrane associated precursors (Stunff et al., J Cell Biochem, 92: 882-899 (2004)). S1P is a metabolic product of sphingolipids, which are ubiquitous phospholipids found in all eukaryotic cell types. S1P is produced intracellularly and released upon appropriate stimulation. The predominant cellular sources of S1P include platelets and tissue mast cells. S1P synthesis begins with the conversion of endogenous membrane-derived sphingomyelin to ceramide (CER) by sphinogmyelinase, then to sphingosine by ceremidase. Sphingosine is then converted to S1P via phosphorylation by one of two sphingosine kinases (SphK1 or SphK2) (Spiegel and Milstien, Nat Rev Mol Cell Biol, 4: 397-407 (2003)). Whereas ceramide and sphingosine have been associated with cell growth arrest and apoptosis, S1P has been shown to be important in cell growth and survival. S1P is an unusual lipid in that it can act both intracellularly and extracellularly. Intracellular S1P binds to putative endoplasmic reticulum-associated receptors to facilitate the release of intracellular stores of calcium during cell activation. Most of these phospholipids compounds fail to effectively discriminate between different S1P receptors and have poor physicochemical properties, which limits their potential use as pharmaceutical agents. Thus, there exists a need for compounds, which are not phospholipids that bind or otherwise regulate S1P receptors and can also selectively bind to a specific S1P receptor. Extracellular S1P acts as a potent ligand for a family of G-protein coupled receptors (GPCRs). The best characterized actions of S1P are mediated by its binding to a class of GPCRs known as the endothelial differentiation gene-1 (EDG-1) family. To date, a total of five EDG receptors, EDG-1, EDG-5, EDG-3, EDG-6 and EDG-8 have been shown to bind S1P with high affinity and specificity. These receptors are also designated S1P1, S1P2, S1P3, S1P4 and S1P5, respectively (Sanchez and Hla, J Cell Biochem, 92: 913-922 (2004)). The existence of multiple receptors for S1P implies that its functions may be considerably diverse. S1P receptors have a widespread cellular and tissue distribution and are well-conserved in human and rodent species (Spiegel and Milstien, Biochim Biophys Acta, 484:107-116 (2000); and Hla, Prostaglandins Other Lipid Mediat, 64: 135-142 (2001)). S1P receptors can couple to different G-proteins to elicit a wide variety of cellular responses (Goetzl and Rosen, J Clin Invest, 114:1531-1537 (2004); and Spiegel and Milstien, Nat Rev Mol Cell Biol, 4: 397-407 (2003)). Studies with transfected cells have shown that S1P1 receptors signal exclusively through G _i proteins to inhibit adenylate cyclase and stimulate mitogen activated protein kinase (MAPK) in addition to PTX sensitive activation of phospholipase C (PLC). S1P2 and S1P3 receptors can signal through multiple G protein subtypes including G _i , G _q and G _12/13 . S1P2 activates Ras/MAPK via Gi but unlike S1P1 stimulates PLC via a PTX insensitive G _q and activates Rho. S1P4 primarily activates G _i and the MAPK pathway and S1P5 is coupled to G _i and G ₁₂ to inhibit adenylate cyclase but does not stimulate MAPK. Several studies have indicated that many cell types express more than one subtype of S1P receptor and that multiple S1P receptors may cooperate to lead to particular biological responses to S1P. As a result, S1P is implicated in a large variety of physiological functions. S1P3 receptors are broadly expressed on cell types of the immune system including monocytes, B and T lymphocytes, dendritic cells, mast cells, natural killer cells, and eosinophils (Lin and Broyce, Adv Immunol, 89: 141-167 (2006)). S1P3 has also been found to mediate vasoconstriction of cerebral arteries and induce bradycardia and hypertension in rodents (Salomone et al., Eur J Pharmacol, 469: 125-34 (2003)). In vascular endothelial cells, S1P stimulates cell proliferation and migration in vitro and angiogenesis in vivo (Lee et al., Cell, 99: 301-21 (1999)). These S1P actions were mediated via S1P1 and S1P3 receptors. S1P1 has also been implicated in tumour angiogenesis and tumour growth. In contrast, S1P2 exerts inhibitory effects on endothelial migration, morphogenesis and angiogenesis in vivo. In addition, lung endothelial barrier function is enhanced by S1P activation of S1P1 and endothelial permeability is increased by activation of S1P2. In epithelial cells, S1P3 receptors have been shown to induce reorganization of tight junctions and consequently compromise lung barrier integrity. While functions of S1P4 and S1P5 are less well-understood, the S1P4 receptor has been shown to be localized in haematopoietic cells and tissue (Graeler et al., Curr Top Microbiol Immunol, 246: 131-6 (1999)) and the S1P5 receptor has been shown to be primarily a neuronal receptor with some expression in lymphoid tissue in rodents but with a broader expression pattern in human tissue (Im et al., J Biol Chem, 275(19): 14281-6 (2000); Neidernberg et al., Biochem Pharmacol, 64: 1243-50 (2002)). SUMMARY OF THE INVENTION There remains a need for new treatments and therapies for asthma. The invention provides compounds, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and combinations thereof, which compounds are S1P3 modulators. The invention further provides   methods of treating, preventing, or ameliorating inflammatory lung diseases, comprising administering to a subject in need thereof an effective amount of an S1P3 modulator. According to a first aspect of the invention, Embodiment 1, there is provided a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R ¹ is Het, which may be unsubstituted or substituted on a nitrogen atom by R ⁵ and independently on one or two carbon atoms by R ⁶ ; or R ¹ is a phenyl ring, which may be unsubstituted or substituted by one or two substituents R ^6a ; R ² is H, halo or cyano; R ³ is H, halo, cyano, Het ¹ or Het ¹ C ₁ -C ₆ alkyl-; and Het ¹ may be unsubstituted or substituted on a nitrogen atom by R ⁷ and independently on one or two carbon atoms by R ⁸ ; and R ⁴ is H, halo or cyano; or R ⁴ is H, halo, cyano, Het ¹ or Het ¹ C ₁ -C ₆ alkyl-; and Het ¹ may be unsubstituted or substituted on a nitrogen atom by R ⁷ and independently on one or two carbon atoms by R ⁸ ; and R ³ is H, halo or cyano; R ⁵ is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ -C ₄ alkyl O(O)C-, C ₁ -C ₄ alkyl OC(O)C ₁ -C ₄ alkyl-, or C ₃ - C ₈ cycloalkyl; wherein C ₁ -C ₆ alkyl may be unsubstituted or may be substituted with one or more substituents selected from halo, -OH, –NR ⁹ R ¹⁰ , C ₁ -C ₄ alkoxy or C ₃ -C ₈ cycloalkyl; each R ⁶ is independently halo, C ₁ -C6alkyl, -OH, –NR ⁹ R ¹⁰ , CN, C ₁ -C6alkoxy, C ₁ -C6alkylS-, C ₁ - C ₄ alkylO(O)C-, H(O)C-, C ₃ -C ₈ cycloalkyl, –or Het, wherein C ₁ -C ₆ alkyl and C ₁ -C ₆ alkoxy may be   unsubstituted or substituted with one or more halo, -OH, –NR ⁹ R ¹⁰ ,C ₁ -C ₄ alkoxy or C ₃ - C ₈ cycloalkyl; or two R ⁶ groups, or R ⁶ and R ⁵ , may be taken together with the atoms to which they are attached to form a C ₃ -C ₈ cycloalkyl, phenyl, Het ¹ , or Het ² ring, and wherein the C ₃ -C ₈ cycloalkyl, phenyl, Het ¹ , or Het ² ring may be unsubstituted or may be substituted by one or two substituents selected from halo and C ₁ -C ₆ alkyl; R ^6a is halo, C ₁ -C ₆ alkyl, haloC ₁ -C ₆ alkyl, haloC ₁ -C ₆ alkoxy or cyano; R ⁷ is C ₁ -C ₆ alkyl, haloC ₁ -C ₆ alkyl, hydroxyC ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxyC ₁ -C ₆ alkyl-, R ⁹ OC(O)C ₁ -C ₆ alkyl- , H ₂ NC(O)C ₁ -C ₆ alkyl-, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkylC ₁ -C ₆ alkyl-, Het ² C ₁ -C ₆ alkyl-; each R ⁸ is independently halo, C ₁ -C ₆ alkyl, haloC ₁ -C ₆ alkyl, hydroxyC ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, C ₁ - C ₆ alkoxyC ₁ -C ₆ alkyl-, R ⁹ (O) ₂ C-, R ⁹ OC(O)C ₁ -C ₆ alkyl-, H ₂ NC(O)C ₁ -C ₆ alkyl-, C ₃ -C ₈ cycloalkyl, C ₃ - C ₈ cycloalkylC ₁ -C ₆ alkyl-, Het ² , Het ² C ₁ -C ₆ alkyl-; Het is a 5 or 6 membered heteroaryl ring containing a) 1 oxygen or sulphur atom and 0,1 or 2 nitrogen atoms, or b) 1 to 2 nitrogen atoms; Het ¹ is a 5 or 6 membered heteroaryl ring containing a) 1 oxygen or sulphur atom and 0, 1 or 2 nitrogen atoms, or b) 1, 2, 3 or 4 nitrogen atoms; Het ² is a 4 to 7 membered saturated heterocyclic ring containing 1 or 2 heteroatoms selected from N, O and S; and Het ² may be unsubstituted or substituted with one or two substituents selected from halo, C ₁ -C ₄ alkyl and C ₁ -C ₄ alkoxy, wherein the alkyl and alkoxy groups may be unsubstituted or substituted with one or more groups selected from halo, hydroxy and –NR ⁹ R ¹⁰ ; and R ⁹ and R ¹⁰ are each independently H, or C ₁ -C ₆ alkyl, wherein the alkyl may be unsubstituted or substituted with one or more halo. In another embodiment, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound according to the definition of formula (I), or a pharmaceutically acceptable salt thereof, or subformulae thereof and one or more pharmaceutically acceptable carriers.   In another embodiment, the invention provides a combination, in particular a pharmaceutical combination, comprising a therapeutically effective amount of the compound according to the definition of formula (I), or a pharmaceutically acceptable salt thereof, or subformulae thereof and one or more therapeutically active agent. In another embodiment, the invention provides a method of modulating S1P3 receptor activity in a subject, comprising administering to the subject a therapeutically effective amount of the compound according to the definition of formula (I), or a pharmaceutically acceptable salt thereof, or subformulae thereof and one or more pharmaceutically acceptable carriers. In another embodiment, the invention provides a method of treating asthma in a subject, comprising administering to the subject a therapeutically effective amount of the compound according to the definition of formula (I), or a pharmaceutically acceptable salt thereof, or subformulae thereof and one or more pharmaceutically acceptable carriers. DETAILED DESCRIPTION Various embodiments of the invention are described herein. It will be recognized that features specified in each embodiment may be combined with other specified features to provide further embodiments of the present invention. The invention therefore provides as Embodiment 1 a compound of the formula (I) or a pharmaceutically acceptable salt thereof, as defined hereinabove. Embodiment 2. A compound according to Embodiment 1 or a pharmaceutically acceptable salt thereof, wherein R ¹ is Het, which may be unsubstituted or substituted on a nitrogen atom by R ⁵ and independently on one or two carbon atoms by R ⁶ ; and R ⁵ and R ⁶ are as defined in Embodiment 1. Embodiment 3. A compound according to Embodiment 1 or 2 or a pharmaceutically acceptable salt thereof, wherein R ¹ is selected from thiazolyl, thiadiazolyl, isoxazolyl pyrazolyl, imidazolyl, pyridinyl, pyrazinyl and pyridazinyl; and wherein R ¹ is substituted on a nitrogen atom by R ⁵ and independently on one or two carbon atoms by R ⁶ ; and R ⁵ and R ⁶ are as defined in Embodiment 1. Embodiment 4. A compound according to Embodiment 1, 2 or 3 or a pharmaceutically acceptable salt thereof, wherein R ¹ is selected from   indicates the point of attachment; and R ⁵ and R ⁶ are as defined in Embodiment 1. Embodiment 5. A compound according to Embodiment 1, 2, 3 or 4 or a pharmaceutically acceptable salt thereof, wherein R ¹ is selected from indicates the point of attachment; and R ⁵ and R ⁶ are as defined in Embodiment 1.   Embodiment 6. A compound according to Embodiment 1, 2, 3, 4 or 5, or a pharmaceutically acceptable salt thereof, wherein R ⁵ is absent (unsubstituted ring) or is selected from methyl and ethylOC(O)methyl-; and wherein each R ⁶ is independently absent (unsubstituted ring) or is selected from bromo, chloro, fluoro, cyano, methyl, ethyl, propyl (n-propyl or isopropyl), butyl (preferably tert-butyl), pentyl (preferably neopentyl), trifluoromethyl, trifluoromethoxy, methylthio, isopropylthio, hydroxypropanyl, methoxymethyl, cyclopropyl, cyclobutyl, furanyl, pyridinyl, H(O)C-, methyl(O) ₂ C-, ethyl(O) ₂ C-, tert-butyl(O) ₂ C-, and ethylOC(O)methyl-; or two R ⁶ groups may be taken together with the atoms to which they are attached to form a cyclopentyl, cyclohexyl, cycloheptyl, phenyl , pyridinyl , pyridizinyl or tetrahydropyranyl ring, which cyclopentyl, cyclohexyl, cycloheptyl, phenyl , pyridinyl , pyridizinyl or tetrahydropyranyl ring is unsubstituted or is substituted by one chloro, fluoro or methyl. Embodiment 7. A compound according to Embodiment 1, 2, 3, 4, 5 or 6, or a pharmaceutically acceptable salt thereof, wherein R ⁵ is absent (unsubstituted ring) or is methyl or ethylOC(O)methyl-; and wherein each R ⁶ is independently absent (unsubstituted ring) or is selected from bromo, chloro, fluoro, cyano, methyl, ethyl, propyl (n-propyl or isopropyl), butyl (preferably tert-butyl), pentyl (preferably neopentyl), trifluoromethyl, trifluoromethoxy, methylthio, isopropylthio, hydroxypropanyl, methoxymethyl, cyclopropyl, cyclobutyl, furanyl, pyridinyl, H(O)C-, methyl(O) ₂ C-, ethyl(O) ₂ C-, tert-butyl(O) ₂ C-, and ethylOC(O)methyl-. Embodiment 8. A compound according to Embodiment 1, 2, 3, 4, 5, 6 or 7, or a pharmaceutically acceptable salt thereof, wherein R ² is H, R ³ is cyano and R ⁴ is cyano; or R ² is cyano, R ³ is H and R ⁴ is cyano; or R ² is H, R ³ is cyano and R ⁴ is H. Embodiment 9. A compound according to Embodiment 1, 2, 3, 4, 5, 6 or 7, or a pharmaceutically acceptable salt thereof, wherein R ² is H, R ⁴ is H and R ³ is Het ¹ C ₁ -C ₆ alkyl-; or R ² is H, R ⁴ is H and R ³ is Het ¹ ;   Het ¹ is unsubstituted or may be substituted on a nitrogen atom by R ⁷ and independently on one or two carbon atoms by R ⁸ ; and wherein R ⁷ and R ⁸ are as defined in Embodiment 1. Embodiment 10. A compound according to Embodiment 1, 2, 3, 4, 5, 6, 7 or 9, or a pharmaceutically acceptable salt thereof, wherein R ² is H, R ⁴ is H and R ³ is selected from: and wherein R ⁷ and R ⁸ are as defined in Embodiment 1. Embodiment 11. A compound according to Embodiment 9 or 10, or a pharmaceutically acceptable salt thereof, wherein R ⁷ is C ₁ -C ₄ alkyl (including deuterated C ₁ -C ₄ alkyl, preferably trideuterio-methyl), haloC ₁ -C ₆ alkyl-, hydroxyC ₁ -C ₄ alkyl-, C ₁ -C ₄ alkoxyC ₁ -C ₄ alkyl-, HOC(O)C ₁ -C ₄ alkyl-, H ₂ NC(O)C ₁ -C ₄ alkyl-, C ₃ - C ₆ cycloalkyl, C ₃ -C ₆ cycloalkylC ₁ -C ₄ alkyl or morpholinoC ₁ -C ₄ alkyl-; and R ⁸ is H, halo or C ₁ -C ₄ alkyl. Embodiment 12. A compound according to Embodiment 1, 2, 3, 4, 5 , 67, 8, 9, 10 or 11, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a racemate or has stereochemistry is as shown in formula (Ia) or (Ib);   Embodiment 13. A compound according to Embodiment 1, 2, 3, 4, 5 ,67, 8, 9, 10, 11 or 12, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) has stereochemistry is as shown in formula (Ia) or (Ib) above. The present disclosure includes compounds of formula (I) wherein the stereochemistry is as shown in formula (Ic) and (Id): wherein R1, R2, R3 and R4 are as defined in the Embodiments hereinabove. Embodiment 14. A compound of formula (I) according to Embodiment 1, selected from: 2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5-(trifluoromethyl)-1H-pyrazol-3- yl)acetamide; N-(5-Chloropyridin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-difluo rocyclopentyl)acetamide;N-(5- Chlorothiazol-2-yl)-2-(4-cyanophenyl)-2-(3,3-difluorocyclope ntyl)acetamide; 2-(3-cyanophenyl)- 2-(3,3-difluorocyclopentyl)-N-(5-fluorothiazol-2-yl)acetamid e;2-(3-Cyanophenyl)-2-(3,3- difluorocyclopentyl)-N-(5-fluorothiazol-2-yl)acetamide; N-(5-Chloropyrazin-2-yl)-2-(4- cyanophenyl)-2-(3,3-difluorocyclopentyl)acetamide; Ethyl 2-(5-(2-(3,5-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamido)-3-(trifluoromethyl)-1H-pyrazo l-1-yl)acetate; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5,6-dih ydro-4H-cyclopenta[d]thiazol-2- yl)acetamide; N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3 ,3-difluorocyclopentyl) acetamide; N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-difluo rocyclopentyl)acetamide; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5-(trifluoromethyl)-1H-pyrazol-3- yl)acetamide ; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trif luoromethyl)isoxazol-5-yl)acetamide; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-(trif luoromethyl)pyrazin-2-yl)acetamide; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(4,5,6,7 -tetrahydrobenzo[d]thiazol-2- yl)acetamide;   N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanophenyl )-2-(3,3- difluorocyclopentyl)acetamide; 2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-(trif luoromethyl)pyridin-2-yl)acetamide; N-(3-Cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(3,3-d ifluorocyclopentyl)acetamide; N-(3- Cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-(3,3-diflu orocyclopentyl)acetamide; N-(5-Chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-(3,3-difluo rocyclopentyl)acetamide; N-(5- Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-difluorocyc lopentyl)acetamide; 2-(3,5- Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trifluorome thyl)-1,2,4-thiadiazol-5- yl)acetamide; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trif luoromethyl)-1,2,4-thiadiazol-5- yl)acetamide; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(thiazol o[5,4-b]pyridin-2-yl)acetamide; 2- (3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(triflu oromethyl)isoxazol-5-yl)acetamide; Ethyl 2-(5-(2-(3,4-dicyanophenyl)-2-(3,3-difluorocyclopentyl)aceta mido)-3-(trifluoromethyl)-1H- pyrazol-1-yl)acetate; 2-(4-Cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trifluor omethyl)isoxazol-5-yl)acetamide; N-(6-Chloropyridazin-3-yl)-2-(3,5-dicyanophenyl)-2-(3,3-difl uorocyclopentyl) acetamide; N-(5- Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,5-dicyanophenyl)-2-( 3,3-difluorocyclopentyl)acetamide; 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-(trif luoromethyl)-1,3,4-thiadiazol-2- yl)acetamide; 2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-N-(5-chlorothiazol-2- yl)-2-(3,3- difluorocyclopentyl)acetamide; 2-(4-((1H-Tetrazol-1-yl)methyl)phenyl)-N-(5-chlorothiazol-2- yl)-2-(3,3- difluorocyclopentyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-( 3,3-difluorocyclopentyl) acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-( 3,3-difluorocyclopentyl) acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -fluoropyridin-4-yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(1 -methyl-1H-pyrazol-4- yl)phenyl)acetamide ; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(p yridin-4-yl)phenyl)acetamide; N-(5- Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(furan- 3-yl)phenyl)acetamideN-(5- Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(pyrimi din-5-yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(1 -((tetrahydro-2H-pyran-4-yl)methyl)- 1H-pyrazol-4-yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(6 -fluoropyridin-3-yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(1 -(2,2,2-trifluoroethyl)-1H-pyrazol-4- yl)phenyl)acetamide;   2-(4-(1H-1,2,4-Triazol-1-yl)phenyl)-N-(5-chlorothiazol-2-yl) -2-(3,3-difluorocyclopentyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(1 -(difluoromethyl)-1H-tetrazol-5- yl)phenyl)acetamide; N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(difluoromethyl)-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(1-methyl-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(2-fluoroethyl)-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(4-(2-(cyclopropylmethyl)-2H-tetr azol-5-yl)phenyl)-2-(3,3- difluorocyclopentyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(methoxymethyl)-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(difluoromethyl)-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -isopropyl-2H-tetrazol-5- yl)phenyl)acetamide; 3-(5-(4-(2-((5-Chlorothiazol-2-yl)amino)-1-(3,3-difluorocycl opentyl)-2-oxoethyl)phenyl)-2H- tetrazol-2-yl)propanoic acid; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(2-hydroxyethyl)-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(1 -(methoxymethyl)-1H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -ethyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(4-(2-(2-Amino-2-oxoethyl)-2H-tetrazol-5-yl)phenyl)-N-(5-c hlorothiazol-2-yl)-2-(3,3- difluorocyclopentyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(2-morpholinoethyl)-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide;   N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,3-difluorocyclopentyl )-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano[4,3-d]t hiazol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(2,2,2-trifluoroethyl)-2H-tetrazol-5- yl)phenyl)acetamide; Methyl 4-(tert-butyl)-2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamido)thiazole-5-carboxylate; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(4-(trifluoromethyl)thiazol- 2-yl)acetamide; N-(5-Bromopyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2- methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(6-Chlorobenzo[d]thiazol-2-yl)-2-(3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(5-(trifluoromethyl)pyrazin- 2-yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(5,6-dihydro-4H-cyclopenta[d]thia zol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(3-isopropyl-1,2,4-thiadiazol- 5-yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(4,5-dimethylthiazol-2-yl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; tert-Butyl 2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tet razol-5- yl)phenyl)acetamido)-4-methylthiazole-5-carboxylate; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(3-methylisoxazol-5- yl)acetamid; Ethyl 2-( 2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)acetamido)-4- (trifluoromethyl)thiazole-5-carboxylate; N-(5-Chloropyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(3-isopropylisoxazol-5-yl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Bromopyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(6-fluorobenzo[d]thiazol-2-yl)-2- (4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide;   N-(5-Cyanothiazol-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(3-(trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(3-methyl-1,2,4-thiadiazol-5-yl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(5-methylthiazol-2- yl)acetamide; N-(5-Bromo-4-methylpyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(4-Bromopyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(6-(trifluoromethyl)pyridin- 3-yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(4,5,6,7- tetrahydrobenzo[d]thiazol-2-yl)acetamide; N-(4-Bromothiazol-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(3-propylisoxazol-5- yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(4-(trifluoromethyl)pyridin- 2-yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(3-neopentylisoxazol-5- yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(5-fluoropyridin-2-yl)-2-(4-(2-me thyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(3-ethyl-1,2,4-thiadiazol-5-yl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Bromo-1,3,4-thiadiazol-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-(tert-Butyl)-1,3,4-thiadiazol-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(6-Chloropyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(4-methylbenzo[d]thiazol- 2-yl)acetamide;   N-(Benzo[d]thiazol-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(4-fluoropyridin-2-yl)-2-(4-(2-me thyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chloro-4-methylpyridin-2-yl)-2-(-3,3-difluorocyclopenty l)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(5-(isopropylthio)-1,3,4-thiad iazol-2-yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; N-(6-Chloropyrazin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Cyclopentyl-1,3,4-thiadiazol-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(4-Chloro-5-formylthiazol-2-yl)-2-(3,3-difluorocyclopentyl )-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Cyano-6-methylpyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; Methyl 5-chloro-2-( 2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamido)thiazole-4-carboxylate; N-(2,6-Dichloropyridin-4-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(3-(furan-2-yl)isoxazol-5-yl)-2-( 4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(6-methyl-4,5,6,7- tetrahydrobenzo[d]thiazol-2-yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(5-(methylthio)-1,3,4- thiadiazol-2-yl)acetamide; N-(2-Chloropyridin-4-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(4-methylthiazol-2- yl)acetamide; N-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; N-(6-Chloroimidazo[1,2-b]pyridazin-2-yl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide;   2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(5-(trifluoromethyl)oxazol- 2-yl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(4-methyl-5-(pyridin-3- yl)thiazol-2-yl)acetamide; N-(5-Cyclopropyl-1-methyl-1H-pyrazol-3-yl)-2-(3,3-difluorocy clopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(4-(2-hydroxypropan-2-yl)thiaz ol-2-yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(3-(methoxymethyl)isoxazol-5-y l)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(3-(tert-Butyl)-1-methyl-1H-pyrazol-5-yl)-2-(3,3-difluoroc yclopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; 2-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)p henyl)-N-(5-methylpyrazin-2- yl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(5-(furan-2-yl)-1,3,4-thiadiaz ol-2-yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-N-(6-fluoropyridin-3-yl)-2-(4-(2 -methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(5,6,7,8-tetrahydro-4H- cyclohepta[d]thiazol-2-yl)acetamide; Ethyl 2-(2-(-2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazo l-5-yl)phenyl)acetamido)thiazol- 4-yl)acetate; 2-(3,3-Difluorocyclopentyl)-N-(5-(methoxymethyl)-1,3,4-thiad iazol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; N-(4-Bromophenyl)-2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl -2H-tetrazol-5- yl)phenyl)acetamide; N-(3,4-Dichlorophenyl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phe nyl)-N-(3- (trifluoromethyl)phenyl)acetamide; N-(3-Chloro-4-fluorophenyl)-2-( 3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(3- (trifluoromethoxy)phenyl)acetamide; N-(3-Chloro-5-fluorophenyl)-2-(3,3-difluorocyclopentyl)-2-(4 -(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide;   N-(3-Bromophenyl)-2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl -2H-tetrazol-5- yl)phenyl)acetamide; N-(3,5-Dichlorophenyl)-2-(3,3-difluorocyclopentyl)-2-(4-(2-m ethyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(3-Chloro-2-fluorophenyl)-2-(3,3-difluorocyclopentyl)-2-(4 -(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(3,5-Bis(trifluoromethyl)phenyl)-2-(3,3-difluorocyclopenty l)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(3-Chloro-4-cyanophenyl)-2-(3,3-difluorocyclopentyl)-2-(4- (2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; 2-( 3,3-Difluorocyclopentyl)-N-(3-fluorophenyl)-2-(4-(2-methyl-2 H-tetrazol-5- yl)phenyl)acetamide; N-(3-Chlorophenyl)-2-(3,3-difluorocyclopentyl)-2-(4-(2-methy l-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chloro-2-fluorophenyl)-2-(3,3-difluorocyclopentyl)-2-(4 -(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-Chloro-2-methylphenyl)-2-(3,3-difluorocyclopentyl)-2-(4 -(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and N-(2,5-Dichlorophenyl)-2-(3,3-difluorocyclopentyl)-2-(4-(2-m ethyl-2H-tetrazol-5- yl)phenyl)acetamide; and the pharmaceutically acceptable salts thereof. Embodiment 15. A compound of formula (I) according to Embodiment 1, selected from: (S)-2-(3,5-Dicyanophenyl)-2-((S)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (S)-2-(3,5-dicyanophenyl)-2-((R)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (R)-2-(3,5-dicyanophenyl)-2-((S)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (R)-2-(3,5-dicyanophenyl)-2-((R)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; 2-(3-cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-fluorothi azol-2- yl)acetamide; (S)-2-(3-cyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide; (S)-2-(3-cyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide; (R)-2-(3-cyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide; (R)-2-(3-cyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide; (R)-N- (5-Chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R) -3,3-difluorocyclopentyl)acetamide;   (R)-N-(5-chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)- 2-((S)-3,3- difluorocyclopentyl)acetamide; (S)-N-(5-chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)- 2-((R)-3,3- difluorocyclopentyl)acetamide; (S)-N-(5-chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)- 2-((S)-3,3-difluorocyclo pentyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclo pentyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl)acetamide; S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide ; (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide ; (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide ; (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide ; (S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide; (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide; (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide; (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide; (S)-N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanoph enyl)-2-((R)-3,3- difluorocyclopentyl)acetamide; (S)-N-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanoph enyl)-2-((S)-3,3- difluorocyclopentyl)acetamide; (R)-N-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanoph enyl)-2-((R)-3,3- difluorocyclopentyl)acetamide; (R)-N-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanoph enyl)-2-((S)-3,3-difluorocyclopentyl) acetamide; (S)-N-(3-Cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( R)-3,3- difluorocyclopentyl)acetamide;   (S)-N-(3-cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( S)-3,3- difluorocyclopentyl)acetamide; (R)-N-(3-cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( R)-3,3- difluorocyclopentyl)acetamide; (R)-N-(3-cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( S)-3,3- difluorocyclopentyl)acetamide; (S)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (S)- 3,3-difluorocyclopentyl)acetamide; (S)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (R)-3,3- difluorocyclopentyl)acetamide; (R)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (S)-3,3- difluorocyclopentyl)acetamide; (R)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (R)-3,3- difluorocyclopentyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide ; (S)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-difluo rocyclopentyl)acetamide; (S)-2-(3,4- dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N-(3-(trifluo romethyl)-1,2,4-thiadiazol-5- yl)acetamide; (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4-thiadiazol- 5-yl)acetamide; (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4-thiadiazol- 5-yl)acetamide; (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4-thiadiazol- 5-yl)acetamide; (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide; (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide; (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide;   (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide ; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide ; (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Chloro-4-methylthiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-N-(5-chloro-4-methylthiazol-2-yl)-2-((R)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (R)-N-(5-chloro-4-methylthiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (R)-N-(5-chloro-4-methylthiazol-2-yl)-2-((R)-3,3-difluorocyc lo pentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano [4,3-d]thiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-2-((R)-3,3-difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano [4,3-d]thiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (R)-2-((S)-3,3-difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano [4,3-d]thiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (R)-2-((R)-3,3-difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano [4,3-d]thiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- (trifluoromethyl)thiazol-2-yl)acetamide; (S)-N-(5-Bromopyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide;   (S)-N-(6-Chlorobenzo[d]thiazol-2-yl)-2-((S)-3,3-difluorocycl opentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- (trifluoromethyl)pyrazin-2-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5,6-dihydro-4H-cyclop enta[d]thiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-isopropyl-1,2,4-thi adiazol-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(4,5-dimethylthiazol-2 -yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3-methylisoxazol- 5-yl)acetamide; (S)-N-(5-Chloropyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-isopropylisoxazol-5 -yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Bromopyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(6-fluorobenzo[d]thiaz ol-2-yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Cyanothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- (trifluoromethyl)-1,2,4-thiadiazol-5-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-methyl-1,2,4-thiadi azol-5-yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5-methylthiazol-2- yl)acetamide; (S)-N-(5-Bromo-4-methylpyridin-2-yl)-2-((S)-3,3-difluorocycl opentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-N-(4-Bromopyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(6- (trifluoromethyl)pyridin-3-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4,5,6,7- tetrahydrobenzo[d]thiazol-2-yl)acetamide;   (S)-N-(4-Bromothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3-propylisoxazol- 5-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- (trifluoromethyl)pyridin-2-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- neopentylisoxazol-5-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-fluoropyridin-2-yl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-ethyl-1,2,4-thiadia zol-5-yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Bromo-1,3,4-thiadiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-N-(5-(tert-Butyl)-1,3,4-thiadiazol-2-yl)-2-((S)-3,3-difl uorocyclopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-N-(6-Chloropyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- methylbenzo[d]thiazol-2-yl)acetamide; (S)-N-(Benzo[d]thiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(4-fluoropyridin-2-yl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Chloro-4-methylpyridin-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-(isopropylthio)-1,3 ,4-thiadiazol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-N-(6-Chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Cyclopentyl-1,3,4-thiadiazol-2-yl)-2-((S)-3,3-diflu orocyclopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-N-(4-Chloro-5-formylthiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-N-(5-Cyano-6-methylpyridin-2-yl)-2-((S)-3,3-difluorocycl opentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide;   Methyl 5-chloro-2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-meth yl-2H-tetrazol-5- yl)phenyl)acetamido)thiazole-4-carboxylate; (S)-N-(2,6-Dichloropyridin-4-yl)-2-((S)-3,3-difluorocyclopen tyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-ethyl-1,3,4-thiadia zol-2-yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-(furan-2-yl)isoxazo l-5-yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (2S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetra zol-5-yl)phenyl)-N-(6-methyl-4,5,6,7- tetrahydrobenzo[d]thiazol-2-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5-(methylthio)- 1,3,4-thiadiazol-2-yl)acetamide; (S)-N-(2-Chloropyridin-4-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4-methylthiazol-2- yl)acetamide; (S)-N-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-2-((S)-3,3- difluorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-N-(6-Chloroimidazo[1,2-b]pyridazin-2-yl)-2-((S)-3,3-difl uorocyclopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- (trifluoromethyl)oxazol-2-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4-methyl-5- (pyridin-3-yl)thiazol-2-yl)acetamide; (S)-N-(5-Cyclopropyl-1-methyl-1H-pyrazol-3-yl)-2-((S)-3,3-di fluorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(4-(2-hydroxypropan-2- yl)thiazol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-(methoxymethyl)isox azol-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide; (S)-N-(3-(tert-Butyl)-1-methyl-1H-pyrazol-5-yl)-2-((S)-3,3-d ifluorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5-methylpyrazin- 2-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-(furan-2-yl)-1,3,4- thiadiazol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide;   (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(6-fluoropyridin-3-yl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5,6,7,8- tetrahydro-4H-cyclohepta[d]thiazol-2-yl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-(methoxymethyl)-1,3 ,4-thiadiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide; (S)-N-(4-Bromophenyl)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(3,4-Dichlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- (trifluoromethyl)phenyl)acetamide; (S)-N-(3-Chloro-4-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- (trifluoromethoxy)phenyl)acetamide; (S)-N-(3-Chloro-5-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(3-Bromophenyl)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(3,5-Dichlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(3-Chloro-2-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(3,5-Bis(trifluoromethyl)phenyl)-2-((S)-3,3-difluorocy clopentyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide; (S)-N-(3-Chloro-4-cyanophenyl)-2-((S)-3,3-difluorocyclopenty l)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-fluorophenyl)-2-(4- (2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(3-Chlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2-(4- (2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Chloro-2-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-Chloro-2-methylphenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and   (S)-N-(2,5-Dichlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and the pharmaceutically acceptable salts thereof. Embodiment 16. A compound of formula (I) according to Embodiment 1, selected from: (S)-2-(3,5-Dicyanophenyl)-2-((S)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (S)-2-(3,5-dicyanophenyl)-2-((R)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (R)-2-(3,5-dicyanophenyl)-2-((S)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (R)-2-(3,5-dicyanophenyl)-2-((R)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide; (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide; (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -fluoropyridin-4-yl)phenyl)acetamide; N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide ;   N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide; and the pharmaceutically acceptable salts thereof. Embodiment 17. A compound of formula (I) according to Embodiment 1, selected from: (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide; and the pharmaceutically acceptable salts thereof.   Unless specified otherwise, the term “compounds of the present invention” refers to compounds of fomula (I) and subformulae thereof, and salts thereof, as well as all stereoisomers (including diastereoisomers and enantiomers), rotamers, tautomers and isotopically labeled compounds (including deuterium substitutions), as well as inherently formed moieties. As used herein, the term “C _1-6 alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to six carbon atoms, and which is attached to the rest of the molecule by a single bond. The term “C _1-4 alkyl” is to be construed accordingly. Examples of C _1-6 alkyl include, but are not limited to, methyl, ethyl, n-propyl, 1-methylethyl (iso-propyl), n-butyl, 1,1-dimethylethyl (t-butyl) and n- pentyl. As used herein, the term "C _1-6 alkoxy" refers to a radical of the formula -OR _a where R _a is a C _{1- 6} alkyl radical as generally defined above. Examples of C _1-6 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, and hexoxy. As used herein, the term "C _1-6 alkoxyC _1-6 alkyl " refers to a radical of the formula -R _a -O-R _a where each R _a is independently a C _1-6 alkyl radical as defined above. The oxygen atom may be bonded to any carbon atom in either alkyl radical. Examples of C _1-6 alkoxy C _1-6 alkyl include, but are not limited to, methoxy-methyl, methoxy-ethyl, ethoxy-ethyl, 1-ethoxy-propyl and 2-methoxy-butyl. As used herein, the term “C ₁ -C ₄ alkyl O(O)C-“ refers to a C _1-4 alkylcarbonyl radical of the formula R _a -C(=O)- where R _a is a C _1-4 alkyl radical as defined above. As used herein, the term “C ₁ -C ₄ alkyl OC(O)C ₁ -C ₄ alkyl-“ refers to a C _1-4 alkylcarbonylC _1-4 alkyl radical of the formula R _a -C(=O)-R _a- where each R _a is independently a C _1-4 alkyl radical as defined above. The carbon atom of the carbonyl group may be bonded to any carbon atom in either alkyl radical. As used herein, the term "hydroxyC _1-6 alkyl” refers to a C _1-6 alkyl radical as defined above, wherein one of the hydrogen atoms of the C _1-6 alkyl radical is replaced by OH. Examples of hydroxyC _1-6 alkyl include, but are not limited to, hydroxy-methyl, 2-hydroxy-ethyl, 2-hydroxy- propyl, 3-hydroxy-propyl and 5-hydroxy-pentyl. As used herein, the term "C _3-8 cycloalkyl" refers to a stable non-aromatic saturated monocyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, having from three to eight carbon atoms, and which is attached to the rest of the molecule by a bond. The term "C _3-   6cycloalkyl" is to be construed accordingly. Examples of C ₃ - ₈ cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl , cyclohexyl and cycloheptyl. As used herein, the term "C _3-8 cycloalkylC _1-6 alkyl" refers to a stable non-aromatic saturated monocyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, having from three to eight carbon atoms, and which is attached to the rest of the molecule by a C _1-6 alkyl radical as defined above. The term "C _3-6 cycloalkylC _1-4 alkyl" is to be construed accordingly. Examples of C _3-8 cycloalkylC _1-6 alkyl include, but are not limited to, cyclopropyl-methyl, cyclobutyl- ethyl, and cyclopentyl-propyl. "Halo" or "Halogen" refers to bromo, chloro, fluoro or iodo. As used herein, the term "haloC _1-6 alkyl" refers to C _1-6 alkyl radical, as defined above, substituted by one or more halo radicals, as defined above. Examples of haloC _1-6 alkyl include, but are not limited to, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1- fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl and 1-bromomethyl-2-bromoethyl. As used herein, the term “heterocyclic” refers to a stable saturated 4-,5-, 6- or 7-membered non- aromatic monocyclic ring radical which comprises 1 or 2 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded via a carbon atom or heteroatom. Examples of heterocyclyl include, but are not limited to, azetidinyl, oxetanyl, pyrrolinyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, piperidyl, piperazinyl, tetrahydropyranyl, morpholinyl or perhydroazepinyl. As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic ring radical which comprises 1, 2, 3 or 4 heteroatoms as defined in Embodiment 1. The heteroaryl radical may be bonded via a carbon atom or heteroatom. Examples of heteroaryl include, but are not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl. As used herein, the term "Het ¹ C _{1 -6} alkyl" refers to a heteroaryl radical as defined above, which is attached to the rest of the molecule by a C _1-6 alkyl radical as defined above.  Depending on the choice of the starting materials and procedures, the compounds of formula (I) and subformulae thereof, can be present in the form of one of the possible isomers or as mixtures thereof, for example as pure optical isomers, or as isomer mixtures, such as racemates and diastereoisomer mixtures, depending on the number of asymmetric carbon atoms. The present invention is meant to include all such possible isomers, including racemic mixtures, diasteriomeric mixtures and optically pure forms. Optically active (R)- and (S)-   isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis- or trans-configuration. All tautomeric forms are also intended to be included. As used herein, the terms “salt” or “salts” refers to an acid addition or base addition salt of a compound of the invention. “Salts” include in particular “pharmaceutical acceptable salts”. The term “pharmaceutically acceptable salts” refers to salts that retain the biological effectiveness and properties of the compounds of this invention and, which typically are not biologically or otherwise undesirable. In many cases, the compounds of the present invention are capable of forming acid and/or base salts by virtue of the presence of amino and/or carboxyl groups or groups similar thereto. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, the salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium, potassium, sodium, calcium and magnesium salts. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like. Certain organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine and tromethamine. Embodiment 18. A compound of formula (I) which is Example 2: (S)-N-(5-Chlorothiazol-2-yl)-2- (3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl) acetamide   in acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide/hydrobromide, bicarbonate/carbonate, bisulfate/sulfate, camphorsulfonate, caprate, chloride/hydrochloride, chlortheophyllonate, citrate, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide/iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, malonate, mandelate, mesylate, methylsulphate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate trifenatate,trifluoroacetate or xinafoate salt form. Embodiment 19. A compound of formula (I) which is selected from: (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; in acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide/hydrobromide, bicarbonate/carbonate, bisulfate/sulfate, camphorsulfonate, caprate, chloride/hydrochloride, chlortheophyllonate, citrate, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide/iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, malonate, mandelate, mesylate, methylsulphate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate trifenatate,trifluoroacetate or xinafoate salt form. Embodiment 20. A compound of formula (I) which is selected from: (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and   (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; in acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide/hydrobromide, bicarbonate/carbonate, bisulfate/sulfate, camphorsulfonate, caprate, chloride/hydrochloride, chlortheophyllonate, citrate, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide/iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, malonate, mandelate, mesylate, methylsulphate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate trifenatate,trifluoroacetate or xinafoate salt form. Embodiment 21. A compound of formula (I) which is 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)-N-(3-(trifluoromethyl)isoxazol-5-yl )acetamidein acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide/hydrobromide, bicarbonate/carbonate, bisulfate/sulfate, camphorsulfonate, caprate, chloride/hydrochloride, chlortheophyllonate, citrate, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide/iodide, isethionate, lactate, lactobionate, laurylsulfate, malate, maleate, malonate, mandelate, mesylate, methylsulphate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate trifenatate,trifluoroacetate or xinafoate salt form. Embodiment 22. A compound of formula (I) which is (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4- dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl) acetamide in sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, copper, isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine or tromethamine salt form. Embodiment 23. A compound of formula (I) which is selected from:(S)-N-(5-chlorothiazol-2-yl)- 2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5 -yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide;   in sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, copper, isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine or tromethamine salt form. Embodiment 24. A compound of formula (I) which is selected from: (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; in sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, copper, isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine or tromethamine salt form. Embodiment 25. A compound of formula (I) which is 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)-N-(3-(trifluoromethyl)isoxazol-5-yl )acetamide in sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, copper, isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine or tromethamine salt form. Any formula given herein is also intended to represent unlabeled forms as well as isotopically labeled forms of the compounds. lsotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, and chlorine, such as ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ F ³¹ P, ³² P, ³⁵ S, ³⁶ Cl, ¹²³ I, ¹²⁴ I, ¹²⁵ I respectively. The invention includes various isotopically labeled compounds as defined herein, for example those into which radioactive isotopes, such as ³ H and ¹⁴ C, or those into which non-radioactive isotopes, such as ² H and ¹³ C are present. Such isotopically labelled compounds are useful in metabolic studies (with ¹⁴ C), reaction kinetic studies (with, for example ² H or ³ H), detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in radioactive treatment of patients. In particular, an ¹⁸ F or labeled compound may be particularly desirable for PET or SPECT studies. Isotopically-labeled compounds of formula (I) can generally be prepared   by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples and Preparations using an appropriate isotopically- labeled reagents in place of the non-labeled reagent previously employed. Further, substitution with heavier isotopes, particularly deuterium (i.e., ² H or D) may afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements or an improvement in therapeutic index. It is understood that deuterium in this context is regarded as a substituent of a compound of the formula (I). The concentration of such a heavier isotope, specifically deuterium, may be defined by the isotopic enrichment factor. The term "isotopic enrichment factor" as used herein means the ratio between the isotopic abundance and the natural abundance of a specified isotope. If a substituent in a compound of this invention is denoted deuterium, such compound has an isotopic enrichment factor for each designated deuterium atom of at least 3500 (52.5% deuterium incorporation at each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation). In one Embodiment there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, according to any preceding Embodiment, wherein the compound is unlabeled. Pharmaceutically acceptable solvates in accordance with the invention include those wherein the solvent of crystallization may be isotopically substituted, e.g. D ₂ O, d ₆ -acetone, d ₆ -DMSO. Compounds of the invention, i.e. compounds of formula (I) that contain groups capable of acting as donors and/or acceptors for hydrogen bonds may be capable of forming co-crystals with suitable co-crystal formers. These co-crystals may be prepared from compounds of formula (I) by known co-crystal forming procedures. Such procedures include grinding, heating, co-subliming, co-melting, or contacting in solution compounds of formula (I) with the co-crystal former under crystallization conditions and isolating co-crystals thereby formed. Suitable co-crystal formers include those described in WO 2004/078163. Hence the invention further provides co-crystals comprising a compound of formula (I). As used herein, the term "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, absorption delaying agents, salts, preservatives, drug stabilizers, binders, excipients, disintegration agents, lubricants, sweetening agents, flavoring agents, dyes, and the like and combinations thereof, as would be known to those skilled in the   art (see, for example, Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp.1289- 1329). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in the therapeutic or pharmaceutical compositions is contemplated. The term "a therapeutically effective amount" of a compound of the present invention refers to an amount of the compound of the present invention that will elicit the biological or medical response of a subject, for example, reduction or inhibition of an enzyme or a protein activity, or ameliorate symptoms, alleviate conditions, slow or delay disease progression, or prevent a disease, etc. In one non-limiting embodiment, the term “a therapeutically effective amount” refers to the amount of the compound of the present invention that, when administered to a subject, is effective to (1) at least partially alleviate, inhibit, prevent and/or ameliorate a condition, or a disorder or a disease (i) mediated by S1P3, or (ii) associated with S1P3 activity, or (iii) characterized by activity (normal or abnormal) of S1P3; or (2) reduce or inhibit the activity of S1P3; or (3) reduce or inhibit the expression of S1P3. In another non-limiting embodiment, the term “a therapeutically effective amount” refers to the amount of the compound of the present invention that, when administered to a cell, or a tissue, or a non-cellular biological material, or a medium, is effective to at least partially reducing or inhibiting the activity of S1P3; or at least partially reducing or inhibiting the expression of S1P3. As used herein, the term “subject” refers to an animal. Typically the animal is a mammal. A subject also refers to for example, primates (e.g., humans, male or female), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds and the like. In certain embodiments, the subject is a primate. In yet other embodiments, the subject is a human. As used herein, the term “inhibit”, "inhibition" or “inhibiting” refers to the reduction or suppression of a given condition, symptom, or disorder, or disease, or a significant decrease in the baseline activity of a biological activity or process. As used herein, the term “treat”, “treating" or "treatment" of any disease or disorder refers in one embodiment, to ameliorating the disease or disorder (i.e., slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In another embodiment “treat”, "treating" or "treatment" refers to alleviating or ameliorating at least one physical parameter including those which may not be discernible by the patient. In yet another embodiment, “treat”, "treating" or "treatment" refers to modulating the disease or disorder, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both. In yet another embodiment, “treat”, "treating" or "treatment" refers to preventing or delaying the onset or development or progression of the disease or disorder.   As used herein, a subject is “in need of” a treatment if such subject would benefit biologically, medically or in quality of life from such treatment. As used herein, the term "a,” "an,” "the” and similar terms used in the context of the present invention (especially in the context of the claims) are to be construed to cover both the singular and plural unless otherwise indicated herein or clearly contradicted by the context. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. "such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. Any asymmetric atom (e.g., carbon or the like) of the compound(s) of the present invention can be present in racemic or enantiomerically enriched, for example the (R)-, (S)- or (R,S)- configuration. In certain embodiments, each asymmetric atom has at least 50 % enantiomeric excess, at least 60 % enantiomeric excess, at least 70 % enantiomeric excess, at least 80 % enantiomeric excess, at least 90 % enantiomeric excess, at least 95 % enantiomeric excess, or at least 99 % enantiomeric excess in the (R)- or (S)- configuration. Substituents at atoms with unsaturated double bonds may, if possible, be present in cis- (Z)- or trans- (E)- form. Accordingly, as used herein a compound of the present invention can be in the form of one of the possible isomers, rotamers, atropisomers, tautomers or mixtures thereof, for example, as substantially pure geometric (cis or trans) isomers, diastereomers, optical isomers (antipodes), racemates or mixtures thereof. Any resulting mixtures of isomers can be separated on the basis of the physicochemical differences of the constituents, into the pure or substantially pure geometric or optical isomers, diastereomers, racemates, for example, by chromatography and/or fractional crystallization. Any resulting racemates of final products or intermediates can be resolved into the optical antipodes by known methods, e.g., by separation of the diastereomeric salts thereof, obtained with an optically active acid or base, and liberating the optically active acidic or basic compound. In particular, a basic moiety may thus be employed to resolve the compounds of the present invention into their optical antipodes, e.g., by fractional crystallization of a salt formed with an optically active acid, e.g., tartaric acid, dibenzoyl tartaric acid, diacetyl tartaric acid, di-O,O'-p-toluoyl tartaric acid, mandelic acid, malic acid or camphor-10-sulfonic acid.   Racemic products can also be resolved by chiral chromatography, e.g., high pressure liquid chromatography (HPLC) using a chiral adsorbent. Furthermore, the compounds of the present invention, including their salts, can also be obtained in the form of their hydrates, or include other solvents used for their crystallization. The compounds of the present invention may inherently or by design form solvates with pharmaceutically acceptable solvents (including water); therefore, it is intended that the invention embrace both solvated and unsolvated forms. The term "solvate" refers to a molecular complex of a compound of the present invention (including pharmaceutically acceptable salts thereof) with one or more solvent molecules. Such solvent molecules are those commonly used in the pharmaceutical art, which are known to be innocuous to the recipient, e.g., water, ethanol, and the like. The term "hydrate" refers to the complex where the solvent molecule is water. The compounds of the present invention, including salts, hydrates and solvates thereof, may inherently or by design form polymorphs. The compounds of the present invention may be prepared by the routes described in the following Schemes or the Examples. Compounds of the present invention where R ¹ , R ² , R ³ and R ⁴ are as defined in embodiment 1 may be prepared according to Schemes 1 and 2. Scheme 1 Step (a) involves reaction of a methyl benzene with ethyl chloroformate in a suitable solvent such as diglyme with a suitable base such as lithium hexamethyldisilazide at a suitable temperature such as –78ºC.   Step (b) involves reaction of the phenyl acetate with cyclopent-2-enone in a suitable solvent such as THF with a suitable base such as tetra-n-butylammonium fluoride at a suitable temperature such as 0°C to room temperature. Step (c) involves fluorination of the 2-(3-oxocyclopentyl)-2-phenylacetate with diethylaminosulfur trifluoride in a suitable solvent such as DCM at a suitable temperature such as room temperature. Step (d) involves the hydrolysis of the ethyl ester group which is well known in the art. For example, a compound is treated in a suitable solvent such as THF with aqueous LiOH at a suitable temperature such as room temperature. Step (e) involves reaction of the amine with an acid in a suitable solvent such as DMF with a suitable base such as diisopropylethylamine with a suitable amide coupling reagent such as (1- [bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridi nium 3-oxid hexafluorophosphate) at a suitable temperature such as room temperature or reaction of the acid with oxalyl chloride and DMF in a suitable solvent such as DCM followed by addition of the amine with a suitable base such as diisopropylethylamine at a suitable temperature such as room temperature. Scheme 2 Where preferred conditions for Steps (a) to (d) are as listed below – Step (a): To a mixture of 3,5-dibromobenzoic acid (1 eq) and DMF (a few drops) in toluene was added dropwise oxalyl chloride (2 eq) at room temperature. The reaction mixture was stirred at room temperature for 2 h until it was clear. The solvent was then removed and the residue was dissolved in THF. The resulting solution was cooled to –30°C and triethylamine (1.5 eq) was added followed by a solution of diazomethane in Et ₂ O (3 eq). The resulting mixture was allowed to warm to room temperature and stirred for 2 h. Acetic acid solution (10%) was added to quench the reaction followed by ethyl acetate. The organic phase was separated and washed with saturated Na ₂ CO ₃ solution, water and brine. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was washed with hexane/ethyl acetate (10:1) to afford the diazo compound as a yellow solid. This was used in the next step without further purification.   Step (b): A solution of diazo compound (1eq) in THF/water (10:1) was heated to 65°C and a mixture of silver acetate (0.4 eq) in triethylamine (2.0 eq) was added portionwise. The reaction mixture was stirred at 65°C until the diazo compound disappeared by TLC. The mixture was cooled to room temperature and treated sequentially with aqueous sodium bicarbonate solution and ethyl acetate. The solid was filtered off and the aqueous phase was separated and washed with ethyl acetate. The aqueous phase was adjusted to pH 2-3 with 1M aqueous hydrochloric acid and DCM was added. The organic phase was separated and the aqueous phase was extracted with DCM. The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated under reduced pressure. The residue was triturated with ethyl acetate/hexane (10:1) to give the phenyl acetic acid as a white solid. Step (c): To a solution of the phenyl acetic acid (1 eq) in ethanol was added dropwise thionyl chloride (2 eq) at 0°C. The reaction mixture was refluxed for 3 h and then cooled to room temperature. The solvent was removed and ethyl acetate (200 mL) was added. The resulting solution was washed with saturated aqueous Na ₂ CO ₃ solution, water and brine. The organic phase was dried (sodium sulfate) and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to give the ethyl ester. Step (d): A mixture of ethyl ester (1.2 eq), Zn(CN) ₂ (1 eq) and Pd(PPh ₃ ) ₄ (0.06 eq) in DMF was stirred at 80°C for 3 h under nitrogen. The mixture was cooled to room temperature and then treated sequentially with ethyl acetate and water. The solid was filtered and the organic phase was separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with aqueous NH4OH solution (5%), dried (sodium sulfate) and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc 10:1 to 2:1) to give the di-nitrile as a white solid. Compounds of the present invention where R ³ is Het ¹ and R ² and R ⁴ are H, and where R ¹ is as defined in embodiment 1 may be prepared from compounds of the invention where R ³ is cyano or bromo according to Schemes 3 and 4. The skilled person will recognize that an analogous route may also be used to prepare compounds of the present invention where R ⁴ is Het ¹ and R ² and R ³ are H, from compounds of the invention where R ⁴ is cyano or bromo. Scheme 3

Step (a) involves reaction of a phenyl acetamide with trimethylsilylazide and dibutyltin oxide in a suitable solvent such as toluene at a suitable temperature such as 80°C. Step (b) involves alkylation of the tetrazole with an R ⁷ halide in a suitable solvent such as DMF in the presence of a suitable base such as diisopropylethylamine at a suitable temperature such as room temperature. Scheme 4 Step (a) involves reaction of a phenyl acetamide with a boronic acid or a heteroaromatic nitrogen compound with a suitable transition metal catalyst such as palladium or copper with a suitable base such as sodium or potassium carbonate in a suitable solvent such acetonitrile or toluene as at a suitable microwave temperature such as 140°C. When R ³ is Het ¹ (C ₁ -C ₆ )alkyl and R ⁴ is H, the phenyl acetate (A) may be prepared according to Scheme 5. Scheme 5   Step (a) involves reaction of a methylene bromide phenyl acetate with suitable heteroaryl group, such as tetrazole, in the presence of a suitable base such as potassium carbonate in a suitable solvent such as DMF at a suitable temperature such as 80°C. The invention further includes any variant of the present processes, in which an intermediate product obtainable at any stage thereof is used as starting material and the remaining steps are carried out, or in which the starting materials are formed in situ under the reaction conditions, or in which the reaction components are used in the form of their salts or optically pure material. Compounds of the invention and intermediates can also be converted into each other according to methods generally known to those skilled in the art. In another aspect, the present invention provides a pharmaceutical composition comprising a compound of the present invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In a further embodiment, the composition comprises at least two pharmaceutically acceptable carriers, such as those described herein. For purposes of the present invention, unless designated otherwise, solvates and hydrates are generally considered compositions. Preferably, pharmaceutically acceptable carriers are sterile. The pharmaceutical composition can be formulated for particular routes of administration such as oral administration, parenteral administration, and rectal administration, etc. In addition, the pharmaceutical compositions of the present invention can be made up in a solid form (including without limitation capsules, tablets, pills, granules, powders or suppositories), or in a liquid form (including without limitation solutions, suspensions or emulsions). The pharmaceutical compositions can be subjected to conventional pharmaceutical operations such as sterilization and/or can contain conventional inert diluents, lubricating agents, or buffering agents, as well as adjuvants, such as preservatives, stabilizers, wetting agents, emulsifiers and buffers, etc. Typically, the pharmaceutical compositions are tablets or gelatin capsules comprising the active ingredient together with one or more of: a) diluents, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine; b) lubricants, e.g., silica, talcum, stearic acid, its magnesium or calcium salt and/or polyethyleneglycol; for tablets also c) binders, e.g., magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone; if desired d) disintegrants, e.g., starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and e) absorbents, colorants, flavors and sweeteners. Tablets may be either film coated or enteric coated according to methods known in the art.   Suitable compositions for oral administration include an effective amount of a compound of the invention in the form of tablets, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use are prepared according to any method known in the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable preparations. Tablets may contain the active ingredient in admixture with nontoxic pharmaceutically acceptable excipients which are suitable for the manufacture of tablets. These excipients are, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example, starch, gelatin or acacia; and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets are uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate can be employed. Formulations for oral use can be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin or olive oil. Certain injectable compositions are aqueous isotonic solutions or suspensions, and suppositories are advantageously prepared from fatty emulsions or suspensions. Said compositions may be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, they may also contain other therapeutically valuable substances. Said compositions are prepared according to conventional mixing, granulating or coating methods, respectively, and contain about 0.1-75%, or contain about 1-50%, of the active ingredient. Suitable compositions for transdermal application include an effective amount of a compound of the invention with a suitable carrier. Carriers suitable for transdermal delivery include absorbable pharmacologically acceptable solvents to assist passage through the skin of the host. For example, transdermal devices are in the form of a bandage comprising a backing member, a reservoir containing the compound optionally with carriers, optionally a rate controlling barrier to deliver the compound of the skin of the host at a controlled and predetermined rate over a prolonged period of time, and means to secure the device to the skin.   Suitable compositions for topical application, e.g., to the skin and eyes, include aqueous solutions, suspensions, ointments, creams, gels or sprayable formulations, e.g., for delivery by aerosol or the like. Such topical delivery systems will in particular be appropriate for dermal application, e.g., for the treatment of skin cancer, e.g., for prophylactic use in sun creams, lotions, sprays and the like. They are thus particularly suited for use in topical, including cosmetic, formulations well-known in the art. Such may contain solubilizers, stabilizers, tonicity enhancing agents, buffers and preservatives. As used herein a topical application may also pertain to an inhalation or to an intranasal application. They may be conveniently delivered in the form of a dry powder (either alone, as a mixture, for example a dry blend with lactose, or a mixed component particle, for example with phospholipids) from a dry powder inhaler or an aerosol spray presentation from a pressurised container, pump, spray, atomizer or nebuliser, with or without the use of a suitable propellant. The present invention further provides anhydrous pharmaceutical compositions and dosage forms comprising the compounds of the present invention as active ingredients, since water may facilitate the degradation of certain compounds. Anhydrous pharmaceutical compositions and dosage forms of the invention can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. An anhydrous pharmaceutical composition may be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions are packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastics, unit dose containers (e. g., vials), blister packs, and strip packs. The invention further provides pharmaceutical compositions and dosage forms that comprise one or more agents that reduce the rate by which the compound of the present invention as an active ingredient will decompose. Such agents, which are referred to herein as "stabilizers,” include, but are not limited to, antioxidants such as ascorbic acid, pH buffers, or salt buffers, etc. The compounds of formula I in free form or in pharmaceutically acceptable salt form, exhibit valuable pharmacological properties, e.g. S1P3 modulating properties, e.g. as indicated in vitro and in vivo tests as provided in the next sections, and are therefore indicated for therapy or for use as research chemicals, e.g. as tool compounds. Compounds of the invention may be useful in the treatment of inflammatory lung diseases, including: asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia.   Thus, as a further embodiment, the present invention provides the use of a compound of formula (I) or or a pharmaceutically acceptable salt thereof, or subformulae thereof, in therapy. In a further embodiment, the therapy is selected from a disease which may be treated by inhibition of S1P3. In another embodiment, the disease is selected from the afore-mentioned list, suitably asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia, more suitably asthma. Thus, as a further embodiment, the present invention provides a compound of formula (I) or or a pharmaceutically acceptable salt thereof, or subformulae thereof, for use in therapy. In a further embodiment, the therapy is selected from a disease which may be treated by inhibition of S1P3. In another embodiment, the disease is selected from the afore-mentioned list, suitably asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia, more suitably asthma. In another embodiment, the invention provides a method of treating a disease which is treated by inhibition of S1P3 comprising administration of a therapeutically acceptable amount of a compound of formula (I) or or a pharmaceutically acceptable salt thereof, or subformulae thereof. In a further embodiment, the disease is selected from the afore-mentioned list, suitably asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia, more suitably asthma. Thus, as a further embodiment, the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or subformulae thereof, for the manufacture of a medicament. In a further embodiment, the medicament is for treatment of a disease which may be treated by inhibition of S1P3. In another embodiment, the disease is selected from the afore-mentioned list, suitably asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia, more suitably asthma. Embodiment 26. A compound of formula (I) which is (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide, or a pharmaceutically acceptable salt thereof, for use in the treatment of inflammatory lung diseases, including: asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia.   Embodiment 27. A compound of formula (I) which is selected from: (S)-N-(5-chlorothiazol-2-yl)- 2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5 -yl)phenyl)acetamide; (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; or a pharmaceutically acceptable salt thereof, for use in the treatment of inflammatory lung diseases, including: asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia. Embodiment 28. A compound of formula (I) which is selected from: (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; and (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide; or a pharmaceutically acceptable salt thereof, for use in the treatment of inflammatory lung diseases, including: asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia. Embodiment 29. A compound of formula (I) which is 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)-N-(3-(trifluoromethyl)isoxazol-5-yl )acetamide, or a pharmaceutically acceptable salt thereof, for use in the treatment of inflammatory lung diseases, including: asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pulmonary fibrosis and pneumonia. The pharmaceutical composition or combination of the present invention can be in unit dosage of about 1-1000 mg of active ingredient(s) for a subject of about 50-70 kg, or about 1-500 mg or about 1-250 mg or about 1-150 mg or about 0.5-100 mg, or about 1-50 mg of active ingredients. The therapeutically effective dosage of a compound, the pharmaceutical composition, or the   combinations thereof, is dependent on the species of the subject, the body weight, age and individual condition, the disorder or disease or the severity thereof being treated. A physician, clinician or veterinarian of ordinary skill can readily determine the effective amount of each of the active ingredients necessary to prevent, treat or inhibit the progress of the disorder or disease. The above-cited dosage properties are demonstrable in vitro and in vivo tests using advantageously mammals, e.g., mice, rats, dogs, monkeys or isolated organs, tissues and preparations thereof. The compounds of the present invention can be applied in vitro in the form of solutions, e.g., aqueous solutions, and in vivo either enterally, parenterally, advantageously intravenously, e.g., as a suspension or in aqueous solution. The dosage in vitro may range between about 10 ^-3 molar and 10 ^-9 molar concentrations. A therapeutically effective amount in vivo may range depending on the route of administration, between about 0.1-500 mg/kg, or between about 1-100 mg/kg. The activity of a compound according to the present invention can be assessed by the following in vitro & in vivo methods. The S1P3 receptor activity of the agents of the invention has been determined in vitro. The ability of compounds to antagonise S1P activity at the S1P3 receptor was examined using the PathHunter™ Beta-Arrestin assay. The PathHunter™ Flash Detection kit is an assay for the measurement of Enzyme Fragment Complementation (EFC) activity in PathHunter™ cells expressing both the GPCR of interest conjugated to the Enzyme Acceptor (EA) and Beta-arrestin conjugated to the ProLink™ tag. Upon receptor activation and phosphorylation, Beta-arrestin is recruited to the receptor, forcing interaction of the EA and ProLink and allowing complementation between the two fragments to occur. This can then be measured by the addition of a hydrolysable substrate and generation of a chemiluminescent signal. PathHunter® Beta-arrestin CHO-K1 cells stably expressing human S1P3 receptors were plated at a density of 1000cells/ well in a 384-well View Plate. Serial dilutions of test compounds were performed in a 384-well clear polystyrene plate. The test compounds were added to the S1P3 cells and the assay plate incubated for 30mins at 37°C. An EC ₈₀ concentration of S1P was then added to the assay plate for 1.5 hours at 37°C to ensure equilibrium was attained. Flash detection reagent was added to the assay plate and incubated for a further 30mins at 37°C and the plate was then read using a Perkin Elmer EnVision. Data were analysed using GraphPad Prism 6 by fitting a four parameter logistic curve to generate IC ₅₀ values for each compound.   Compounds of the examples, herein below, generally have S1P3 Kb values in the beta-arrestin assays below 10µM. Table 1 provides a list of exemplified compounds with their IC ₅₀ values. Table 1       10.46 0.54   For compounds that were tested in the assay more than once, the data is presented as an average.   The compound of the present invention may be administered either simultaneously with, or before or after, one or more other therapeutic agent. The compound of the present invention may be administered separately, by the same or different route of administration, or together in the same pharmaceutical composition as the other agents. A therapeutic agent is, for example, a chemical compound, peptide, antibody, antibody fragment or nucleic acid, which is therapeutically active or enhances the therapeutic activity when administered to a patient in combination with a compound of the invention. In one embodiment, the invention provides a product comprising a compound of formula (I) and at least one other therapeutic agent as a combined preparation for simultaneous, separate or sequential use in therapy. In one embodiment, the therapy is the treatment of a disease or condition mediated by S1P3 Products provided as a combined preparation include a composition comprising the compound of formula (I) and the other therapeutic agent(s) together in the same pharmaceutical composition, or the compound of formula (I) and the other therapeutic agent(s) in separate form, e.g. in the form of a kit. In one embodiment, the invention provides a pharmaceutical composition comprising a compound of formula (I) and another therapeutic agent(s). Optionally, the pharmaceutical composition may comprise a pharmaceutically acceptable carrier, as described above. In one embodiment, the invention provides a kit comprising two or more separate pharmaceutical compositions, at least one of which contains a compound of formula (I). In one embodiment, the kit comprises means for separately retaining said compositions, such as a container, divided bottle, or divided foil packet. An example of such a kit is a blister pack, as typically used for the packaging of tablets, capsules and the like. The kit of the invention may be used for administering different dosage forms, for example, oral and parenteral, for administering the separate compositions at different dosage intervals, or for titrating the separate compositions against one another. To assist compliance, the kit of the invention typically comprises directions for administration. In the combination therapies of the invention, the compound of the invention and the other therapeutic agent may be manufactured and/or formulated by the same or different manufacturers. Moreover, the compound of the invention and the other therapeutic may be brought together into a combination therapy: (i) prior to release of the combination product to physicians (e.g. in the case of a kit comprising the compound of the invention and the other therapeutic agent); (ii) by the physician themselves (or under the guidance of the physician)   shortly before administration; (iii) in the patient themselves, e.g. during sequential administration of the compound of the invention and the other therapeutic agent. Accordingly, the invention provides the use of a compound of formula (I) for treating a disease or condition mediated by S1P3, wherein the medicament is prepared for administration with another therapeutic agent. The invention also provides the use of another therapeutic agent for treating a disease or condition mediated by S1P3, wherein the medicament is administered with a compound of formula (I). The invention also provides a compound of formula (I) for use in a method of treating a disease or condition mediated by S1P3, wherein the compound of formula (I) is prepared for administration with another therapeutic agent. The invention also provides another therapeutic agent for use in a method of treating a disease or condition mediated S1P3, wherein the other therapeutic agent is prepared for administration with a compound of formula (I). The invention also provides a compound of formula (I) for use in a method of treating a disease or condition mediated by S1P3, wherein the compound of formula (I) is administered with another therapeutic agent. The invention also provides another therapeutic agent for use in a method of treating a disease or condition mediated by S1P3, wherein the other therapeutic agent is administered with a compound of formula (I). The invention also provides the use of a compound of formula (I) for treating a disease or condition mediated by S1P3, wherein the patient has previously (e.g. within 24 hours) been treated with another therapeutic agent. The invention also provides the use of another therapeutic agent for treating a disease or condition mediated by S1P3, wherein the patient has previously (e.g. within 24 hours) been treated with a compound of formula (I). The following examples are intended to illustrate the invention and are not to be construed as being limitations thereon. Temperatures are given in degrees Celsius. If not mentioned otherwise, all evaporations are performed under reduced pressure, typically between about 15 mm Hg and 100 mm Hg (= 20-133 mbar). The structure of final products, intermediates and starting materials is confirmed by standard analytical methods, e.g., microanalysis and spectroscopic characteristics, e.g., MS, IR, NMR. Abbreviations used are those conventional in the art. All starting materials, building blocks, reagents, acids, bases, dehydrating agents, solvents, and catalysts utilized to synthesis the compounds of the present invention are either commercially available or can be produced by organic synthesis methods known to one of ordinary skill in the   art. Further, the compounds of the present invention can be produced by organic synthesis methods known to one of ordinary skill in the art as shown in the following examples. From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims. General Conditions: Mass spectra were run on LCMS systems using electrospray ionization. These were either Agilent 1100 HPLC/Micromass Platform Mass Spectrometer combinations or Waters Acquity UPLC with SQD Mass Spectrometer. [M+H] ⁺ refers to mono-isotopic molecular weights. NMR spectra were run on Bruker AVANCE 400MHz or 500MHz NMR spectrometers using ICON-NMR. Spectra were measured at 298K and were referenced using the solvent peak. The following examples are intended to illustrate the invention and are not to be construed as being limitations thereon. Temperatures are given in degrees centigrade. If not mentioned otherwise, all evaporations are performed under reduced pressure, preferably between about 15 mm Hg and 30 mm Hg (= 20-133 mbar). The structure of final products, intermediates and starting materials is confirmed by standard analytical methods, e.g., microanalysis and spectroscopic characteristics, e.g., MS, IR, NMR. Abbreviations used are those conventional in the art. If not defined, the terms have their generally accepted meanings. Abbreviations: aq. aqueous br broad BuOH butanol Celite® diatomaceous earth filter material d doublet dd doublet of doublets DCM dichloromethane DIPEA diisopropylethylamine DMF N,N-dimethylformamide DMSO dimethylsulfoxide Et ₂ O diethyl ether EtOAc ethyl acetate EtOH ethanol   h hour(s) HATU O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium hexafluorophosphate HPLC High Performance Liquid Chromatography IPA iso-propyl alcohol KOAc Potassium acetate KOtBu Potassium tert-butoxide LCMS liquid chromatography and mass spectrometry MeOH methanol MeCN acetonitrile MP macroporous MS mass spectrometry m multiplet min minute ml/mL milliliter(s) m/z mass to charge ratio NMR nuclear magnetic resonance Pd(PPh ₃ ) ₂ Cl ₂ bis(triphenylphosphine)palladium(II) dichloride PS polymer supported Rac racemic Rt retention time RT room temperature s singlet sat. saturated SCX-2 strong cation exchange (e.g. Isolute® SCX-2 columns from Biotage) SFC supercritical fluid chromatography t triplet TBAF tetrabutylammonium fluoride TBME methyl-tert-butyl ether TEA triethylamine TFA trifluoroacetic acid THF tetrahydrofuran TLC thin layer chromatography Referring to the examples that follow, compounds of the preferred embodiments were synthesized using the methods described herein, or other methods, which are known in the art.   The various starting materials, intermediates and compounds of the preferred embodiments may be isolated and purified, where appropriate, using conventional techniques such as precipitation, filtration, crystallization, evaporation, distillation and chromatography. Unless otherwise stated, all starting materials are obtained from commercial suppliers and used without further purification. Salts may be prepared from compounds by known salt-forming procedures. It should be understood that the organic compounds according to the preferred embodiments may exhibit the phenomenon of tautomerism. As the chemical structures within this specification can only represent one of the possible tautomeric forms, it should be understood that the preferred embodiments encompasses any tautomeric form of the drawn structure. Where microwave heating was employed, this was carried out using a Biotage Initiator Sixty microwave in dedicated reaction vials at the temperature shown and for the time indicated. If not indicated otherwise, the analytical LCMS conditions are as follows: Method 2minLowpHv01 Column: Waters Acquity CSH 1.7µm, 2.1 x 50mm Temperature: 50°C Mobile Phase: A: Water +0.1% Formic Acid B: Acetonitrile +0.1% Formic Acid Flow rate: 1.0mL/min Gradient: 0.0min 5%B, 0.2-1.55min 5-98%B, 1.55-1.75min 98%B, 1.75-1.8min 98-5%B Method 2minLowpHv03: Column: Waters Acquity CSH 1.7µm, 2.1 x 50mm Temperature: 50°C Mobile Phase: A: Water +0.1% Formic Acid B: Acetonitrile +0.1% Formic Acid Flow rate: 1.0mL/min Gradient: 0.0min 5%B, 0.2-1.8min 5-98%B, 1.8-2.1min 98%B, 2.1-2.3min 98%B Method 8minLowpHv01: Column: Waters Acquity CSH 1.7µm, 2.1 x 100mm Temperature: 50 °C Mobile Phase: A: Water +0.1% Formic Acid B: Acetonitrile +0.1% Formic Acid Flow rate: 0.7mL/min Gradient: 0.0min 2%B, 0.3-6.5min 2-98%B, 6.5-7.5min 98%B, 7.5-8.0min 5-98%B Method 10minLowpHv01:   Column: Waters Acquity CSH 1.7µm, 2.1 x 100mm Temperature: 50°C Mobile Phase: A: Water +0.1% Formic Acid B: Acetonitrile +0.1% Formic Acid Flow rate: 0.7mL/min Gradient: 0.0min 2%B, 0.5-8.0min 2-98%B, 8.0-9.0min 98%B, 9.0-9.1min 98-2%B Method 2minLowpH: Column: Waters Acquity CSH 1.7µm, 2.1 x 50mm Temperature: 50 °C Mobile Phase: A: Water +0.1% Formic Acid B: Acetonitrile +0.1% Formic Acid Flow rate: 1.0mL/min Gradient: 0.0min 5%B, 0.2-1.3min 5-98%B, 1.3-1.55min 98%B, 1.55-1.6min 98-5%B Method 2minLC_30_v003: Column Waters BEH C1850x2.1 mm, 1.7 µm Column Temperature 50 °C Eluents A: H ₂ O, B: acetonitrile, both containing 0.1% TFA Flow Rate 0.8 mL/min Gradient 0.25 min 30% B; 30% to 95% B in 1.00 min, 0.25 min 95% B Method 10minLowpH: Column: Waters Acquity CSH 1.7µm, 2.1 x 100mm Temperature: 50 °C Mobile Phase: A: Water +0.1% Formic Acid B: Acetonitrile +0.1% Formic Acid Flow rate: 0.7mL/min Gradient: 0.0min 2%B, 0.5-8.0min 2-98%B, 8.0-9.0min 98%B, 9.0-9.1min 98-2%B Method 2minLowpHv02: Column: Waters Acquity CSH 1.7µm, 2.1 x 50mm Temperature: 50 °C Mobile Phase: A: Water +0.1% TFA B: Acetonitrile +0.1% TFA Flow rate: 1.0mL/min Gradient: 0.0min 5%B, 0.2-1.55min 5-98%B, 1.55-1.75min 98%B, 1.75-1.8min 98-5%B Method 2minLC_v003 Column Waters BEH C1850x2.1 mm, 1.7 µm Column Temperature 50 °C Eluents A: H ₂ O, B: acetonitrile, both containing 0.1% TFA Flow Rate 0.8 mL/min   Gradient 0.20 min 5% B; 5% to 95% B in 1.30 min, 0.25 min 95% B Unless indicated otherwise, preparative HPLC was carried out using an appropriate column and a mobile phase of 0.1% TFA or formic acid in acetonitrile and 0.1 % aqueous TFA or formic acid with an appropriate gradient Example 1 rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-m ethyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid (Intermediate A) (3.1 g, 10.68 mmol) was suspended in DCM (50 ml). DMF (0.01 ml, 0.129 mmol) was added and the reaction mixture was cooled to 0 °C. A solution of oxalyl chloride (1.169 ml, 13.35 mmol) in DCM (20 ml) was added dropwise to the stirred reaction mixture over 1 hour. The reaction mixture was warmed to room temperature and stirred for a further hour.1-Methyl-5-(trifluoromethyl)-1H- pyrazol-3-amine (FluoroChem) (1.852 g, 11.21 mmol) was added to the followed by pyridine (2 ml, 24.73 mmol). The reaction mixture was stirred over night and then partitioned between DCM and water. The aqueous layer was extracted with DCM and the combined organic extracts were washed with 1M HCl aq (x 2), water, sat. NaHCO ₃ (aq), brine, dried over magnesium sulphate, filtered and reduced in vacuo to yield the crude product. The crude product was purified by silica gel column chromatography, eluting with hexane/EtOAc to afford the title compound as stereoisomeric mixture; LC-MS: Rt 5.36 mins; MS m/z 438.2 [M+H]+; Method 10minLowpHv01 ¹ H NMR (400 MHz, chloroform-d) δ 7.98 (dd, 2H) 7.91 (d, 1H), 7.83 (d, 1H), 7.05 (s, 1H), 3.89 (s, 3H), 3.32 (d, 1H), 2.97 (m, 1H), 2.22 (m, 2H) 2.02 – 1.92 (m, 1H), 1.68 – 1.56 (m, 3H). Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter:   Example 1a and 1b (S)-2-(3,5-Dicyanophenyl)-2-((S)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)- 1H-pyrazol-3-yl)acetamide or (S)-2-(3,5-dicyanophenyl)-2-((R)3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)acetamide or (R)-2-(3,5-dicyanophenyl)-2- ((S)3,3-difluorocyclopentyl)-N-(1-methyl-5-(trifluoromethyl) -1H-pyrazol-3-yl)acetamide or (R)-2-(3,5-dicyanophenyl)-2-((R)3,3-difluorocyclopentyl)-N-( 1-methyl-5-(trifluoromethyl)- 1H-pyrazol-3-yl)acetamide Method Details 1: Column: Chiralcel OJ-H 250 x 10 mm, 5 um @ 35degC Mobile phase: 15% Methanol / 85% CO2 Flow: 10 ml/min Detection: UV @ 220 nm Instrument: Berger Minigram SFC1 PEAK 1: SFC Retention Time = 2.85 minutes & PEAK 2: SFC Retention Time = 3.99 minutes Peak 1 was separated using Supercritical Fluid Chromotography using method below to afforded Example 1a and 1b. Method Details 2: Column: Phenomenex LUX-C2, 250 x 10 mm, 5 um   Mobile phase: 15% Isopropanol / 85% CO2 Flow: 10 ml/min Detection: UV @ 220 nm Column Temp: 35 deg C System: Berger Minigram SFC1 Example 1a: Diastereomer 1 of 2-(3,5-dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide SFC Retention Time = 2.98 minutes LC-MS: Rt 5.35 mins; MS m/z 438.1 [M+H]+; Method 10minLowpHv01 1H NMR (400 MHz, Chloroform-d) δ 7.97 (d, 2H), 7.91 (d, 1H), 7.81 (s, 1H), 7.05 (s, 1H), 3.88 (s, 3H), 3.31 (d, 1H), 2.97 (q, 1H), 2.22 (dt, 2H), 2.02 – 1.92 (m, 1H), 1.68 – 1.52 (m, 3H). Example 1b: Diastereomer of of 2-(3,5-dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide SFC Retention Time = 3.55 minutes LC-MS: Rt 5.38 mins; MS m/z 438.1 [M+H]+; Method 10minLowpHv01 1H NMR (400 MHz, Chloroform-d) δ 7.98 (d, 2H), 7.91 (t, 1H), 7.86 (s, 1H), 7.05 (s, 1H), 3.88 (s, 3H), 3.32 (d, 1H), 3.04 – 2.88 (m, 1H), 2.51 (m, 1H), 2.25 – 2.14 (m, 1H), 2.08 (m, 1H), 1.93 (m, 1H), 1.68 – 1.63 (m, 1H), 1.34 (m, 1H). The following examples were prepared by a similar method to that of Example 1, 1a or 1b by replacing 2-(3,5-dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid (Intermediate A) with the appropriate acid (see preparation of intermediates) and 1-methyl-5-(trifluoromethyl)-1H-pyrazol- 3-amine with the appropriate amine (either commercially available or preparations described hereinafter). Example 1.1   rac-N-(5-Chloropyridin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-di fluorocyclopentyl)acetamide LC-MS: Rt = 1.62mins; MS m/z [M+H] ⁺ 401.3; Method 2minLowpH. Example 1.2: rac-N-(5-Chlorothiazol-2-yl)-2-(4-cyanophenyl)-2-(3,3-difluo rocyclopentyl)acetamide LC-MS: Rt = 1.16mins; MS m/z [M+H] ⁺ 382.4; Method 2minLowpH. Example 1.3, 1.3a and 1.3b: rac-2-(3-cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-fluor othiazol-2-yl)acetamide and (S)-2-(3-cyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide or (S)-2-(3-cyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide or (R)-2-(3-cyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide or (R)-2-(3-cyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N-(5-f luorothiazol-2-yl)acetamide   Example 1.3 rac-2-(3-Cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-fluor othiazol-2-yl)acetamide LC- MS: Rt = 0.97mins; MS m/z [M+MeCN] ⁺ 407.1; Method 2minLC_30_v003 Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 25% MeOH / 75% CO ₂ Column: Chiralpak AD-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Diastereomers 1 and 2 of 2-(3-cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-fluorothi azol-2- yl)acetamide, SFC Rt = 3.29 mins and 4.06 mins.   Following removal of diastereomers 1 and 2, separation of the remaining diastereomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 10% isopropanol / 90% CO ₂ Column: Phenomenex LUX-C2, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.3a Diastereomer 3 of 2-(3-cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-fluorothi azol-2- yl)acetamide, SFC Rt = 5.51 mins Example 1.3b Diastereomer 4 of 2-(3-cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-fluorothi azol-2- yl)acetamide, SFC Rt = 7.32 mins Example 1.4: rac-N-(5-Chloropyrazin-2-yl)-2-(4-cyanophenyl)-2-(3,3-difluo rocyclopentyl)acetamide LC-MS: Rt = 1.12mins; MS m/z [M+H] ⁺ 377.3; Method 2minLowpH. Example 1.5: Ethyl 2-(5-(2-(3,5-dicyanophenyl)-2-(3,3-difluorocyclopentyl)aceta mido)-3- (trifluoromethyl)-1H-pyrazol-1-yl)acetate   LC-MS: Rt = 1.13mins; MS m/z 510.5 [M+H] ⁺ ; Method 2minLowpH ¹ H NMR (400 MHz, CDCl3) δ 8.90 (1H, d), 8.0 (2H, m), 7.95 (1H, s), 6.70 (1H, d), 4.90 (2H,m), 4.30 (2H, q), 3.40 (1H, d), 2.95 (1H, m), 2.60-1.60 (5H, m), 1.35 (4H, m). Example 1.6: 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5,6-dih ydro-4H-cyclopenta[d]thiazol- 2-yl)acetamide LCMS: Rt =1.26 mins; MS m/z 413.3 [M+H]+; Method 2minLowpHv01 Example 1.7 N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3 ,3-difluorocyclopentyl) acetamide LCMS :Rt =1.35 mins; MS m/z 421.2 [M+H]+; Method 2minLowpHv01   Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Examples 1.7a and 1.7b (R)-N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)- 2-((R)-3,3- difluorocyclopentyl)acetamide or (R)-N-(5-chloro-4-methylthiazol-2-yl)-2-(3,4- dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)acetamide or(S)-N-(5-chloro-4- methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluor ocyclopentyl)acetamide or (S)- N-(5-chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(( S)-3,3-difluorocyclo pentyl)acetamide SFC Column: Chiralpak IA 250 x 10mm, 5um Mobile phase: 45% Methanol / 55% CO2 Flow: 10 ml/min Detection: UV @ 220 nm System: Berger Minigram SFC2 Example 1.7a Diastereomer 1 of N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3 ,3- difluorocyclopentyl) acetamide SFC Rt= 4.28 minutes. Example 1.7b   Diastereomer 2 of N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3 ,3- difluorocyclopentyl) acetamide SFC Rt= 5.41 minutes. Example 1.8, 1.8a and 1.8b: rac-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-di fluorocyclopentyl)acetamide and (S)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclo pentyl)acetamide or (S)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3- difluorocyclopentyl)acetamide or (R)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3- difluorocyclopentyl)acetamide or (R)-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3- difluorocyclopentyl)acetamide

  Example 1.8 rac-N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-di fluorocyclopentyl)acetamide LC-MS: Rt = 1.11mins; MS m/z [M+H] ⁺ 402.3; Method 2minLowpH. Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 20% iPrOH / 80% CO ₂ Column: Chiralpak AD-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.8a Diastereomer 1 of N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide, SFC Rt = 5.07 mins   Example 1.8b Diastereomer 2 of N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide, SFC Rt = 5.82 mins Diastereomers 3 and 4 of N-(5-chloropyrazin-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide, SFC Rt = 8.18 mins and 15.44 mins. Example 1.9, 1.9aand 1.9b: rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-m ethyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide and (S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)- 1H-pyrazol-3-yl)acetamide or (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)- 1H-pyrazol-3-yl)acetamide or (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)- 1H-pyrazol-3-yl)acetamide or (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (1-methyl-5-(trifluoromethyl)- 1H-pyrazol-3-yl)acetamide

  Example 1.9 rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-m ethyl-5-(trifluoromethyl)-1H- pyrazol-3-yl)acetamide LC-MS: Rt = 1.14mins; MS m/z [M+H] ⁺ 438.3; Method 2minLowpH. Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase: 10% MeOH / 90% CO ₂ Column: Chiralcel OJ-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.9a Diastereomer 1 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide, SFC Rt = 4.22 mins   Following removal of diastereomer 1, separation of the remaining stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase: 20% isopropanol / 80% CO ₂ Column: 2 × Chiralpak AD-H coupled, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.9b Diastereomer 2 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide, SFC Rt = 6.69 mins Diastereomers 3 and 4 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(1-methy l-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide, SFC Rt = 5.80 mins and 7.56 mins. Example 1.10, 1.10a and 1.10b: rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-( trifluoromethyl)isoxazol-5- yl)acetamide and (S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide or (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide or (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide or (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)isoxazol-5- yl)acetamide

  Example 1.10 rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-( trifluoromethyl)isoxazol-5- yl)acetamide LC-MS: Rt = 1.17mins; MS m/z [M-H] ⁺ 423.3; Method 2minLowpH. Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase: 10% MeOH / 90% CO ₂ Column: Chiralcel OJ-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.10a   Diastereomer 1 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide, SFC Rt = 6.23. mins Example 1.10b Diastereomer 2 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide, SFC Rt = 7.55 mins Following removal of diastereomers 1 and 2, separation of the remaining diastereomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 10% isopropanol / 90% CO ₂ Column: Chiralpak AD-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Diastereomers 3 and 4 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide, SFC Rt = 3.95 mins and 5.53 mins. Example 1.11: rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-( trifluoromethyl)pyrazin-2- yl)acetamide LC-MS: Rt = 1.14mins; MS m/z [M-H] ⁺ 436.4; Method 2minLowpH. Example 1.12: 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(4,5,6,7 -tetrahydrobenzo[d]thiazol-2- yl)acetamide   LC-MS: Rt = 1.33mins; MS m/z [M+H] ⁺ 427.2; Method 2minLowpHv01 Example 1.13 rac-N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanoph enyl)-2-(3,3- difluorocyclopentyl)acetamide and LC-MS: Rt = 4.92mins; MS m/z [M+H] ⁺ 414.2; Method 10minLowpH ¹ H NMR (400 MHz, DMSO-d6) δ 12.80 (1H, s), 8.15 (2H, m), 7.90 (1H, m), 3.95 (1H, t), 2.95 (1H, m), 2.35 (1H, m), 2.25-1.85 (4H, m), 1.75-1.25 (2H, m), 1.10 (2H, m), 0.90 (2H, m). Examples 1.13a and 1.13b: (S)-N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanoph enyl)-2-((R)-3,3- difluorocyclopentyl)acetamide or (S)-N-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4- dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)acetamide or (R)-N-(5-cyclopropyl-1,3,4- thiadiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocy clopentyl)acetamide or (R)-N- (5-cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanophenyl)- 2-((S)-3,3-difluorocyclopentyl) acetamide

SFC METHOD DETAILS: Column: Phenomenex LUX C4250 x 10 mm, 5 um @ 35degC Mobile phase: 30% Methanol / 70% CO2 Flow: 10 ml/min Detection: UV @ 220 nm System: Berger Minigram SFC2 Example 1.13a Diastereomer 1 of N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanophenyl )-2-(3,3- difluorocyclopentyl)acetamide First eluted peak SFC Rt= 5.10 minutes. LC-MS: Rt = 1.07mins; MS m/z [M+H] ⁺ 414.4; Method 2minLowpH 1H NMR (400 MHz, CDCl3) δ 14.0 (1H, br), 8.20 (1H, s), 8.0 (1H, d), 7.75 (1H, d), 4.25 (1H, d), 3.0 (1H, m), 2.45 (2H, m), 2.20 (1H, m), 2.10 (1H, m), 1.90 (1H, m), 1.60 (1H, m), 1.30 (3H, d), 1.15 (2H, m). Example 1.13b Diastereomer 2 of N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,4-dicyanophenyl )-2-(3,3- difluorocyclopentyl)acetamide Second eluted peak SFC Rt= 5.80 minutes.   LC-MS: Rt = 1.07mins; MS m/z [M+H] ⁺ 414.4; Method 2minLowpH ¹ H NMR (400 MHz, CDCl3) δ 14.1 (1H, br), 8.20 (1H, s), 8.0 (1H, d), 7.75 (1H, d), 4.25 (1H, d), 3.0 (1H, m), 2.40 (1H, m), 2.25 (1H, m), 2.15 (1H, m), 2.0 (1H, m), 1.60 (3H, m), 1.35 (2H, d), 1.20 (2H, m). Example 1.14: rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-( trifluoromethyl)pyridin-2- yl)acetamide LC-MS: Rt = 1.17 mins; MS m/z [M+H] ⁺ 435.4; Method 2minLowpH ¹ H NMR (400 MHz, DMSO-d6) δ 11.33 (1H, d), 8.75 – 8.69 (1H, m), 8.41 (1H, m), 8.28 – 8.14 (4H, m), 3.97 (1H, dd), 3.00 (1H, m,), 2.36 – 1.84 (4H, m), 1.76 – 1.49 (1H, m), 1.36 – 1.20 (1H, m). Example 1.15 rac-N-(3-Cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(3 ,3- difluorocyclopentyl)acetamide LC-MS: Rt = 1.15mins; MS m/z [M+H] ⁺ 411.5; Method 2minLowpH 1H NMR (400 MHz, CDCl3) δ 9.10 (1H, br), 8.0 (2H, m), 7.95 (1H, s), 6.35 (1H, s), 3.60 (1H, m), 3.50 (1H, d), 3.0 (1H, m), 2.55-1.30 (12H, m). Examples 1.15a and 1.15b:   (S)-N-(3-Cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( R)-3,3- difluorocyclopentyl)acetamide or (S)-N-(3-cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( S)-3,3- difluorocyclopentyl)acetamide or (R)-N-(3-cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( R)-3,3- difluorocyclopentyl)acetamide or (R)-N-(3-cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(( S)-3,3- difluorocyclopentyl)acetamide Examples 1.15a Separation conditions:Column: Chiralpak IA, 250 x 10 mm, 5 um @ 35degC Mobile phase: 10% Methanol / 90% CO2 Flow: 10 ml/min Detection: UV @ 220 nm System: Berger Minigram SFC1 Diastereomer 1 of N-(3-Cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide   First eluted peak SFC Rt= 6.67 minutes. LC-MS: Rt = 1.15mins; MS m/z [M+H] ⁺ 411.6; Method 2minLowpH ¹ H NMR (400 MHz, CDCl3) δ 9.60 (1H, br), 8.05 (2H, s), 7.95 (1H, s), 6.40 (1H, s), 3.60 (2H, m), 3.0 (1H, m), 2.35 (2H, m), 2.20 (4H, m), 2.10 (2H, m), 1.95 (2H, m), 1.60 (2H, m). Examples 1.15a Separation conditions: Column: Chiralcel OJ-H 250 x 10 mm, 5 um @35degC Mobile phase: 25% Methanol / 75% CO2 Flow: 10 ml/min Detection: UV @ 220 nm System: Berger Minigram SFC1 Diastereomer 2 of N-(3-Cyclobutylisoxazol-5-yl)-2-(3,5-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide, Second eluted peak Rt= 7.02 minutes. LC-MS: Rt = 1.15mins; MS m/z [M+H] ⁺ 411.5; Method 2minLowpH ¹ H NMR (400 MHz, CDCl3) δ 9.36 (1H, s), 8.03 (2H, d), 7.94 (1H, t), 6.38 (1H, s), 3.66 – 3.49 (2H, m), 3.10 – 2.94 (1H, m), 2.53 (1H, m), 2.38 (2H, m), 2.31 – 1.82 (7H, m), 1.63 (1H, m). Examples 1.16, 1.16a and 1.16b: rac-N-(3-Cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( 3,3- difluorocyclopentyl)acetamide and (S)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (S)-3,3- difluorocyclopentyl)acetamide or (S)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (R)-3,3- difluorocyclopentyl)acetamide or (R)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (S)-3,3- difluorocyclopentyl)acetamide or (R)-N-(3-cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( (R)-3,3- difluorocyclopentyl)acetamide   Example 1.16 rac-N-(3-Cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-( 3,3- difluorocyclopentyl)acetamide LC-MS: Rt = 1.09mins; MS m/z [M+H] ⁺ 397.4; Method 2minLowpH. Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 40% MeOH / 60% CO ₂ Column: Chiralcel OJ-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.16a Diastereomeric mixture 1 of N-(3-Cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide, SFC Rt = 2.28 mins   Example 1.16b Diastereomeric mixture 2 of N-(3-Cyclopropylisoxazol-5-yl)-2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide, SFC Rt = 3.89 mins Example 1.17: rac-N-(5-Chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-(3,3-di fluorocyclopentyl)acetamide LC-MS: Rt = 1.11mins; MS m/z [M+H] ⁺ 402.3; Method 2minLowpH 1H NMR (400 MHz, CDCl3) δ 9.30 (1H, br), 8.25 (1H, s), 8.0 (3H, m), 7.95 (1H, s), 3.45 (1H, m), 3.0 (1H, m), 2.55-1.30 (6H, m). Examples 1.17a and 1.17b: (S)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide or (S)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide or (R)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide or (R)-N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide

  Examples 1.17a Diastereomer 1 of N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide Separation conditions: Column: Chiralpak IC, 250 x 10 mm, 5 um @ 35degC Mobile phase: 35% Isopropanol / 65% CO2 Flow: 10 ml/min Detection: UV @ 220 nm System: SFC- WATERS INVESTIGATOR First eluted peak SFC Rt= 3.42 minutes. LC-MS: Rt = 1.10mins; MS m/z [M+H] ⁺ 400.4; Method 2minLowpH 1H NMR (400 MHz, CDCl3) δ 9.30 (1H, br), 8.50 (1H, s), 8.30 (1H, s), 8.05 (2H, s), 7.95 (1H, s), 3.50 (1H, d), 3.0 (1H, m), 2.25 (3H, m), 2.0 (1H, m), 1.65 (2H, m). Examples 1.17b   Diastereomer 2 of N-(5-chloropyrazin-2-yl)-2-(3,5-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide Separation conditions: Column: 2 x LUX-C2250 x 10mm, 5um coupled, @ 35degC Mobile phase: 20% Methanol / 80% CO2 Flow: 10 ml/min Detection: UV @ 220 nm System: SFC- WATERS INVESTIGATOR Second eluted peak Rt= 16.42 minutes LC-MS: Rt = 1.10mins; MS m/z [M+H] ⁺ 400.4; Method 2minLowpH 1H NMR (400 MHz, CDCl3) δ 9.30 (1H, br), 8.30 (1H, s), 8.25 (1H, s), 8.0 (2H, s), 7.95 (1H, s), 3.50 (1H, d), 3.0 (1H, m), 2.5 (1H, m), 2.20 (1H, m), 2.10 (1H, m), 1.95 (1H, m), 1.65 (1H, m), 1.35 (1H, m). Example 1.18: rac-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3-di fluorocyclopentyl)acetamide LC-MS: Rt = 1.16 mins; MS m/z [M+H] ⁺ 407.3; Method 2minLowpH 1H NMR (400 MHz, CDCl3) δ 7.90 (1H, s), 7.80 (2H, m), 7.30 (1H, s), 3.55 (1H, d), 3.0 (1H, m), 2.5-1.90 (4H, m), 1.60 (1H, m), 1.35 (1H, m). Example 1.19: rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-( trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide

LC-MS: Rt = 1.16 mins; MS m/z [M+H] ⁺ 442.5; Method 2minLowpH ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 13.83 (1H, s), 8.44 (1H, dt, J = 2.9, 1.5 Hz), 8.21 (2H, dd, J = 5.8, 1.6 Hz), 4.03 (1H, dd, J = 10.9, 8.1 Hz), 3.05 (1H, dt, J = 18.8, 8.9 Hz), 2.26 – 1.29 (6H, m). Examples 1.20, 1.20a and 1.20b rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-( trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide and (S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide or (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide or (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide or (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)-N- (3-(trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide

Example 1.20 rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-( trifluoromethyl)-1,2,4- thiadiazol-5-yl)acetamide LC-MS: Rt = 1.09mins; MS m/z [M-H] ⁺ 440.2; Method 2minLowpH. Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 10% MeOH / 90% CO ₂ Column: Chiralpak AD-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min   Diastereomer 1 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trif luoromethyl)-1,2,4- thiadiazol-5-yl)acetamide, SFC Rt = 3.58 mins Diastereomer 2 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trif luoromethyl)-1,2,4- thiadiazol-5-yl)acetamide, SFC Rt = 4.28 mins Following removal of diastereomers 1 and 2, separation of the remaining diastereomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 15% isopropanol / 85% CO ₂ Column: Chiralcel OD-H, 250 x 10 mm id, 5 µm Detection: UV @ 220nm Flow rate: 10 ml/min Example 1.20a and 1.20b Diastereomers 3 and 4 of 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3- (trifluoromethyl)-1,2,4-thiadiazol-5-yl)acetamide, SFC Rt = 5.54 mins and SFC Rt = 6.85 mins Example 1.21: 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(thiazol o[5,4-b]pyridin-2-yl)acetamide LC-MS: Rt = 1.20mins; MS m/z [M+H]+ 424.3; Method 2minLowpH01 Example 1.22: rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-( trifluoromethyl)isoxazol-5- yl)acetamide   LC-MS: Rt = 1.16 mins; MS m/z [M-H]- 423.2; Method 2minLowpH ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.54 (1H, s), 8.43 (1H, dt, J = 2.9, 1.5 Hz), 8.18 (2H, dd, J = 5.7, 1.5 Hz), 6.74 (1H, d, J = 1.4 Hz), 3.84 (1H, dd, J = 11.0, 6.6 Hz), 3.08 – 2.89 (1H, m), 2.40 – 1.26 (6H, m). Example 1.23: rac-Ethyl 2-(5-(2-(3,4-dicyanophenyl)-2-(3,3-difluorocyclopentyl)aceta mido)-3- (trifluoromethyl)-1H-pyrazol-1-yl)acetate LC-MS: Rt = 1.17mins; MS m/z [M-H] ⁺ 508.2; Method 2minLowpH. Example 1.24: rac-2-(4-Cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trif luoromethyl)isoxazol-5- yl)acetamide   DMF (0.876 µl, 0.011 mmol) and oxalyl chloride chloride (0.109 ml, 1.244 mmol) were added sequentially and dropwise to 2-(4-cyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid(300 mg, 1.131 mmol) in DCM (10 ml). Afer stirring for 1 h at room temperature, 3- (trifluoromethyl)isoxazol-5-amine (430 mg, 2.83 mmol) and pyridine (0.366 ml, 4.52 mmol) were added dropwise and the resulting mixture was stirred at room temperature for 1 h. The reaction mixture was then diluted with DCM, washed with water, dried (MgSO ₄ ) and concentrated under reduced pressure. Purification by flash column chromatography on silica with iso-hex-EtOAc (0- 40%) as eluent gave the isoxazole (298mg, 66%). LC-MS: Rt = 1.19mins; MS m/z [M-H] ⁺ 398.2; Method 2minLowpH. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.87 (1H, v br s), 7.61 (2H, d), 7.42 (2H, d), 6.58 (1H, s), 3.42 (1H, d), 2.89 (1H, mult), 2.45 (1H, mult), 2.20-1.70 (3H, complex mults), 1.50 (1H, complex mult), 1.27 (1H, complex mult) (10-15% minor isomer present, ethyl acetate and hexane-type solvents). Example 1.25: rac-N-(6-Chloropyridazin-3-yl)-2-(3,5-dicyanophenyl)-2-(3,3- difluorocyclopentyl) acetamide LC-MS: Rt = 1.05 mins; MS m/z [M+H] ⁺ 402.7; Method 2minLowpH   ¹ H NMR (400 MHz, DMSO-d6) δ 11.67 (1H, s), 8.45 – 8.31 (2H, m), 8.21 (2H, dd, J = 8.3, 1.6 Hz), 7.88 (1H, d, J = 9.4 Hz), 3.98 (1H, dd, J = 11.1, 9.1 Hz), 2.99 (1H, m), 2.44 – 1.20 (m, 6H). Example 1.26: rac-N-(5-Cyclopropyl-1,3,4-thiadiazol-2-yl)-2-(3,5-dicyanoph enyl)-2-(3,3- difluorocyclopentyl)acetamide LC-MS: Rt = 1.05 mins; MS m/z [M+H] ⁺ 414.4; Method 2minLowpH ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 12.78 (1H, s), 8.42 (1H, dt, J = 2.9, 1.5 Hz), 8.17 (2H, dd, J = 7.0, 1.5 Hz), 3.90 (1H, dd, J = 11.0, 6.8 Hz), 3.06 – 2.92 (1H, m), 2.37 (1H, m, J = 8.3, 4.9 Hz), 2.31 – 1.21 (6H, m), 1.19 – 1.01 (2H, m), 0.99 – 0.90 (2H, m). Example 1.27: rac-2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(5-( trifluoromethyl)-1,3,4- thiadiazol-2-yl)acetamide LC-MS: Rt = 1.15mins; MS m/z [M-H] ⁺ 440.3; Method 2minLowpH. Example 1.28: rac-2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-N-(5-chlorothiazo l-2-yl)-2-(3,3- difluorocyclopentyl)acetamide   2-(4-((2H-Tetrazol-2-yl)methyl)phenyl)-2-(3,3-difluorocyclop entyl)acetic acid (Intermediate I) (50 mg, 0.155 mmol) was dissolved in dry DCM (2 ml) and placed into a N ₂ flushed vial. To this was added 1 drop of DMF, followed by oxalyl chloride (0.016 ml, 0.186 mmol) (gas given off) and the contents left stirring at RT under N ₂ for approximately 30 mins. After this time, 5- chlorothiazol-2-amine.HCl (31.8 mg, 0.186 mmol) was added, followed by pyridine (0.063 ml, 0.776 mmol) and the contents left stirring at room temperature overnight. The contents were diluted with DCM (4 ml) and washed with water (x2), sat. NaHCO ₃ ,1M HCl, brine and the organic layer separated and evaporated under reduced pressure, to give an orange/brown oil. The crude oil was chromatographed on silica gel (12 g) using the Teledyne ISCO system and eluting with a gradient of 0% to 50% acetone/iso-hexane. The product fractions were combined and evaporated to give rac-2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-N-(5-chlorothiazo l- 2-yl)-2-(3,3-difluorocyclopentyl)acetamide as an off white solid. LC-MS: Rt 1.27 mins; MS m/z 439.2 [M+H]+; Method 2minLowpHv01. ¹ H NMR (400 MHz, Chloroform-d) δ 8.55 (1H, s), 7.32 (4H, d, J = 2.5 Hz), 7.26 (1H, d, J = 4.3 Hz, 1H), 5.79 (2H, s), 3.48 (1H, t, J = 11.0 Hz), 3.11 – 2.90 (1H, m), 2.57 – 1.16 (6H, m). Selective NOESY NMR experiment confirmed the compound was the N-2 regioisomer. Example 1.29: 2-(4-((1H-Tetrazol-1-yl)methyl)phenyl)-N-(5-chlorothiazol-2- yl)-2-(3,3- difluorocyclopentyl)acetamide The title compound was prepared analogously to Example 1.28 from rac-Methyl 2-(4-((1H- tetrazol-2-yl)methyl)phenyl)-2-(3-oxocyclopentyl)acetate (Intermediate Ia) and 5-chlorothiazol- 2-amine hydrochloride; LC-MS: Rt 1.18 mins; MS m/z 439.3 [M+H]+; Method 2minLowpHv01   ¹ H NMR (400 MHz, Chloroform-d) δ 8.70 (1H, d, J = 1.5 Hz), 7.35 (2H, d, J = 7.9 Hz), 7.28 – 7.19 (3H, m), 5.59 (2H, s), 3.56 (1H, t, J = 10.4 Hz), 3.11 – 2.89 (1H, m), 2.52 – 1.04 (6H, m). Example 2: (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((S)-3, 3-difluorocyclopentyl) acetamide A stirred solution of (S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)ace tic acid (Intermediate Ba, diastereomer 2) (33.4 g, 115 mmol) in DCM (1000mL) was cooled on an ice/water bath under nitrogen. DMF (0.089 mL, 1.151 mmol) was added in one portion, followed by oxalyl chloride (15 mL, 171 mmol). After stirring at 0°C for 90 minutes, the ice/water bath was removed and a further DMF (250µL) was added. The solution was left to stir for 3 hrs at room temperature. LC-MS analysis of a reaction aliquot quenched in methanol confirmed conversion to the acid chloride was complete. The reaction was concentrated under reduced pressure, to give ~35 g of a viscous orange syrup. The syrup was redissolved in fresh DCM (1000 mL) and 5-chlorothiazol-2-amine hydrochloride (23.62 g, 138 mmol) was added in one portion with stirring under nitrogen, to give a thick suspension. Pyridine (46.5 mL, 575 mmol) was added slowly to give a brown mixture. The reaction was stirred under nitrogen at room temperature for 48 hrs before diluting with DCM (1000m L) and washing consecutively with 1M HCl(aq) (2 x 1000mL), sat.NaHCO(aq) (500mL) and water (500mL). Residual water was removed from the organic solution by passing through a phase separator before concentrating to dryness under reduced pressure, to afford a pale brown sticky foamed solid. Purification was achieved in two stages: Stage 1: The residue was dissolved in DCM (50mL) and loaded as a solution onto a RediSep 750g silica cartridge (conditioned with 20% EtOAc in iso-hexane); isocratic elution with 20% EtOAc in iso-hexane ultimately afforded a pale yellow foam of ~90% target purity. Stage 2: The yellow foam was dissolved in DCM and loaded as a solution onto a RediSep 330g silica cartridge (conditioned with 1% acetic acid in DCM); gradient elution 0-10% TBME in DCM (+1% acetic acid) afforded the product as a yellow oil. This was re-dissolved in DCM and washed consecutively with saturated aqueous NaHCO ₃ , water and brine. Residual water was removed from the organic solution by passing through a phase separator. Concentration to   dryness under reduced pressure and drying under high vacuum at room temperature for several days, gave a pale yellow foam LC-MS: Rt = 4.75 minutes; MS m/z 407.3 [M+H]+ Method 8minLowpHv01 Single peak: Rt = 4.75 minutes; MS ES+ m/z 407.3 [M+H]+ 1H-NMR (400 MHz, CDCl ₃ ) δ 7.88 (1H, s), 7.85 - 7.75 (2H, m), 7.33 (1H, s), 3.55 (1H, d, J = 10.7 Hz), 3.12 - 2.92 (1H, m), 2.60 - 2.35 (1H, m), 2.32 - 1.84 (3H, m), 1.76 - 1.58 (1H, m), 1.46 - 1.27 (1H, m). 19F NMR (376 MHz, CDCl ₃ ) δ -88.56 (d _AB , J _AB = 230.7 Hz), -92.61 (d _AB , J _AB = 230.7 Hz). Example 3: (S)-N-(5-Chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)-3, 3-difluorocyclopentyl) acetamide The diastereomeric composition of N-(5-chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl)acetamide (Example 1.28) was visualised by analytical chiral SFC (Chiralpak AD-3µm (150 x 2.1 mm), isocratic elution: scCO ₂ /methanol 9:1, 0.7 ml/min @ 40°C, UV detection @ 220nm and 254nm). Peak A: Rt = 24.74 minutes; peak B: Rt = 28.13 minutes; peak C: Rt = 38.47 minutes; peak D: Rt = 45.75 minutes. Peak B was isolated from the mixture of diastereomers by preparative chiral SFC over two stages: Stage 1: Chiralcel OJ 5µ (250 x 30mm); scCO ₂ :methanol 2:1 achieved separation of the mixture into pairs of diastereomers: Peak 1 (first eluting) was a mixture of analytical peaks A and C; peak 2 (second eluting) was a mixture of analytical peaks B and D. Stage 2: Chiralpak AD 5µm (250 x 30mm); scCO ₂ :methanol 2:1 achieved separation of peak 2 into its constituent diastereomers: first eluting (analytical peak B); second eluting (analytical peak D. The solid isolated as analytical peak B was suspended in hexane (~20mL) and heated to reflux, before sufficient EtOAc was added to dissolve the suspended solid at reflux. The heat was removed and the solution was left to cool to room temperature overnight. A fine needle-like crystalline precipitate had formed. This precipitate was isolated by filtration, washed with   hexanes and dried under vacuum @40°C for 18hr. Drying gave 520mg of a colourless crystalline solid. Analytical SFC: single peak: Rt = 27.25 minutes LC-MS Rt = 5.41 minutes; MS m/z 405.3 [M+H]- Method 10minLowpHv01; 1H NMR (400MHz, CDCl3) δ 7.88 (1H, s), 7.83 (1H, d, J = 8.1Hz), 7.79 (1H, d, J = 8.1Hz), 7.31 (1H, s), 3.51 (1H, d, J = 9.6Hz), 3.04-2.98 (1H, m), 2.56-2.44 (1H, m), 2.28-2.16 (1H, m), 2.15- 2.03 (1H, m), 1.98-1.85 (1H, m), 1.70-160 (1H, m), 1.41-1.31 (1H, m). Absolute configuration confirmed as (S)-N-(5-chlorothiazol-2-yl)-2-(3,4-dicyanophenyl)-2-((R)- 3,3-difluorocyclopentyl)acetamide by single crystal X-ray. Example 4.0: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-fluoropyridin-4- yl)phenyl)acetamide 2.0 M aqueous sodium carbonate (0.344 ml, 0.689 mmol) was added dropwise to 2- fluoropyridin-4-ylboronic acid (32.3 mg, 0.230 mmol), bis(triphenylphosphine)palladium(II) chloride (8.05 mg, 0.011 mmol) and 2-(4-bromophenyl)-N-(5-chlorothiazol-2-yl)-2-(3,3- difluorocyclopentyl)acetamide in MeCN (1 ml) and the resulting mixture was heated in the microwave at 140°C for 15mins. After allowing to cool to room temperature the reaction was filtered through Celite®. The Celite® was washed with MeCN and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica with iso-hex-EtOAc (0-30%) as eluent followed by reverse phase column chromatography to afford the title compound; LC-MS: Rt = 1.22mins; MS m/z [M-H] ⁺ 452.3; Method 2minLowpH. ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.58-10.13 (1H, v br s), 8.30 (1H, mult), 7.61 (2H, d), 7.44 (2H, d), 7.37 (1H, mult), 7.29 (1H, mult), 7.28 (1H, s), 7.10 (1H, mult), 3.50 (0.4H, d), 3.49 (0.6H, d), 3.05 (1H, mult), 2.55 (0.6H, mult), 2.32-1.34 (5.4H, complex overlapped mults) (60:40 isomer ratio).   The following examples were prepared by a similar method to that of Example 4.0 by replacing 2-fluoropyridin-4-ylboronic acid with the appropriate commercially available boronic acid: Example 4.1: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(1-methyl-1H-pyrazol-4- yl)phenyl)acetamide LCMS: Rt = 1.15mins; MS m/z 437.2 [M+H]+; Method 2minLowpH. Example 4.2: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(pyridin-4- yl)phenyl)acetamide LCMS: Rt = 0.92mins; MS m/z 434.1 [M+H]+; Method 2minLowpH. Example 4.3: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(furan-3-yl)phenyl)acetamide   LCMS: Rt = 1.27mins; MS m/z 423.2 [M+H]+; Method 2minLowpH. Example 4.4: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(pyrimidin-5- yl)phenyl)acetamide LCMS: Rt = 1.11mins; MS m/z 435.2 [M+H]+; Method 2minLowpH Example 4.5: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(1-((tetrahydro-2H-pyran-4- yl)methyl)-1H-pyrazol-4-yl)phenyl)acetamide   LCMS: Rt = 1.19mins; MS m/z 521.3 [M+H]+; Method 2minLowpH Example 4.6: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(6-fluoropyridin-3- yl)phenyl)acetamide LCMS: Rt = 1.22mins; MS m/z 452.3 [M+H]+; Method 2minLowpH Example 4.7: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(1-(2,2,2-trifluoroethyl)-1H- pyrazol-4-yl)phenyl)acetamide LCMS: Rt = 1.20 mins; MS m/z 505.4 [M+H]+; Method 2minLowpH Example 5: rac-2-(4-(1H-1,2,4-Triazol-1-yl)phenyl)-N-(5-chlorothiazol-2 -yl)-2-(3,3- difluorocyclopentyl)acetamide   2-(4-Bromophenyl)-N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocy clopentyl)acetamide (49.2 mg, 0.113 mmol) and (1S, 2S)-N1,N2-dimethylcyclohexane-1,2-diamine (2.97 µl, 0.019 mmol) in DMF (0.5 ml) was dropwise to copper(I) iodide(8.96 mg, 0.047 mmol), 1H-1,2,4-triazole (6.5 mg, 0.094 mmol) and potassium carbonate (27.3 mg, 0.198 mmol) under nitrogen. The resulting mixture was heated at 110°C for 18 h and then allowed to cool to room temperature, diluted with EtOAc and filtered through Celite ^® . After washing with EtOAc, the combined organics were concentrated under reduced pressure and the crude product was purified by flash column chromatography on silica with iso-hex-EtOAc (0-60%) as eluent to give the triazole (7.4mg, 19%). LC-MS: Rt = 1.08mins; MS m/z [M-H] ⁺ 424.3; Method 2minLowpH. ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.73-10.26 (1H, v br s), 8.48 (1H, s), 8.04 (1H, s), 7.57 (2H, d), 7.35 (1H, d), 7.34 (1H, d), 7.22 (0.5H, s), 7.19 (0.5H, s), 3.42 (0.5H, d), 3.39 (0.5H, d), 2.96, (1H, mult), 2.42 (0.5H, mult), 2.25-1.24 (5.5H, complex overlapped mults)(50:50 isomer ratio, significant ethyl acetate present). Example 6: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(1-(difluoromethyl)-1H- tetrazol-5-yl)phenyl)acetamide and N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2- (4-(2-(difluoromethyl)-2H-tetrazol-5-yl)phenyl)acetamide   Difluoroiodomethane in DMF (0.062 ml, 0.165 mmol) was added dropwise to a solution of 2-(4- (1H-tetrazol-5-yl)phenyl)-N-(5-chlorothiazol-2-yl)-2-(3,3-di fluorocyclopentyl)acetamide (Intermediate G) (70 mg, 0.165 mmol) and triethylamine (0.046 ml, 0.330 mmol) in DMF (1 ml) at 0°C. After stirring for 1 h, triethylamine (0.046 ml, 0.330 mmol) and difluoroiodomethane in DMF (0.062 ml, 0.165 mmol) were added and the mixture was allowed to warm to room temperature and stirred for 7 h. Additonal triethylamine (0.046 ml, 0.330 mmol) and difluoroiodomethane in DMF (0.062 ml, 0.165 mmol) were then added and the mixture was stirred at room temperature for 18 h. Further triethylamine (0.046 ml, 0.330 mmol) and difluoroiodomethane in DMF (0.062 ml, 0.165 mmol) were added and the mixture was stirred at room temperature for 3 h and then diluted with DCM and washed with 1 M aqueous hydrochloric acid, water and brine. The crude product was purified by flash column chromatography on silica with iso-hex-EtOAc (0-50%) as eluent followed by flash column chromatography on silica with iso-hex-EtOAc (0-40%) as eluent to give the 1H- (7.4mg, 9%) and 2H-tetrazole (8.9mg, 11%) confirmed by nOe spectroscopy. LC-MS rac-1H-: Rt = 1.16mins; MS m/z [M-H] ⁺ 475.3; Method 2minLowpH. LC-MS rac-2H-: Rt = 1.22mins; MS m/z [M-H] ⁺ 475.3; Method 2minLowpH. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.87 (1H, v br s), 8.31 (0.5H, t), 8.30 (0.5H, t), 7.89 (2H, d), 7.68 (1H, d), 7.67 (1H, d), 7.53 (0.5H, s), 7.52 (0.5H, s), 3.90 (0.5H, d), 3.87 (0.5H, d), 2.99 (1H, mult), 2.40-1.30 (6H, complex overlapped mults)(50:50 isomer ratio, some solvent residues). Example 6.1, 6.1a and 6.1b: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide and (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   To a solution of 2-(4-(1H-tetrazol-5-yl)phenyl)-N-(5-chlorothiazol-2-yl)-2-(3 ,3- difluorocyclopentyl)acetamide (Intermediate G) (50 mg, 0.118 mmol) in DMF (2 ml) was added NaOH (4.71 mg, 0.118 mmol) followed by MeI (7.36 µl, 0.118 mmol). The mixture was stirred at room temperature for 2 hrs. The mixture was diluted with DCM and washed with water. The organic phase was separated using a phase separating column and the solvent was removed under reduced pressure. The crude product was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane to afford the title compound as a racemic mixture; Example 6.1 LC-MS: Rt = 1.15 mins; MS m/z [M-H] ⁺ 439.4; Method 2minLowpH. Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile phase: 45% Isopropanol / 55% CO2 Column: Chiralpak AD-H, 250 x 10 mm, 5 um @ 35degC   Detection: UV @ 220 nm Flow: 10 ml/min Diastereomers 1 and 2 of N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide, SFC Rt = 4.13 mins and 6.89 mins. Following removal of diastereomers 1 and 2, separation of the remaining diastereomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 40% Isopropanol / 60% CO2 Column: Phenomenex LUX-C2, 250 x 10 mm id, 5 µm Detection: UV @ 220 nm Flow rate: 10 ml/min Examples 6.1a Diastereomer 3 of N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide SFC Rt = 3.26 mins. LCMS: Rt= 1.18 mins; MS m/z 439.2 [M+H]+; Method 2minLowpH Examples 6.1b Diastereomer 4 of N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide SFC Rt =.3.91mins LCMS: Rt= 1.18 mins; MS m/z 439.2 [M+H]+; Method 2minLowpH Example 6.2, 6.2a and 6.2b: rac-N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(trideuterio)-2H-tetrazol-5- yl)phenyl)acetamide and (S)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol- 5-yl)phenyl)acetamide or (S)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol- 5-yl)phenyl)acetamide or (R)-N-(5-chlorothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H-tetrazol- 5-yl)phenyl)acetamide or   (R)-N-(5-chlorothiazol-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-( trideuterio)-2H- tetrazol-5-yl)phenyl)acetamide To a solution of 2-(4-(1H-tetrazol-5-yl)phenyl)-N-(5-chlorothiazol-2-yl)-2-(3 ,3-difluorocyclopentyl) acetamide (Intermediate G) (100 mg, 0.235 mmol) in DMF (2 ml) was added triethylamine (0.033 ml, 0.235 mmol) followed by iodomethane-d3 (0.015 ml, 0.235 mmol). The mixture was stirred at room temperature overnight. The resulting mixture was diluted with DCM and washed with 1M HCl, water (4x) and brine. The organic phase was separated using a phase separating column. The crude product was purified by chromatography on silica eluting with a gradient of 0- 50% EtOAc in iso-hexane. The product fractions were collected and solvent was removed under vaccum to afford the title compound; Example 6.2 LCMS: Rt= 1.17mins; MS m/z 442.2 [M+H]+; Method 2minLowpH   Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile phase: 35% Isopropanol / 65% CO2 Column: Chiralpak AD-H, 250 x 10 mm, 5 um @ 35degC Detection: UV @ 220 nm Flow rate: 10 ml/minDiastereomers 1 and 2 of N-(5-chlorothiazol-2-yl)-2-(3,3- difluorocyclopentyl)-2-(4-(2-(trideuterio)-2H-tetrazol-5-yl) phenyl)acetamide, SFC Rt = 6.40 mins and 11.25 mins Following removal of diastereomers 1 and 2, separation of the remaining diastereomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile Phase : 25% Isopropanol / 75% CO2 Column: Phenomenex LUX-C2, 250 x 10 mm id, 5 µm Detection: UV @ 220 nm Flow rate: 10 ml/min Example 6.2a Diastereomer 3 of N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(trideuterio)- 2H-tetrazol-5-yl)phenyl)acetamide, SFC Rt = 5.52 mins LCMS: Rt 1.31 mins; MS m/z 442.2 [M+H]+; Method 2minLowpHv01. Example 6.2b Diastereomer 4 of N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -(trideuterio)- 2H-tetrazol-5-yl)phenyl)acetamide, SFC Rt = 7.18 mins LC/MS Rt 1.29 mins; MS m/z 442.3 [M+H]+; Method 2minLowpHv01. Example 6.3 rac-N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide and (S)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or   (R)-N-(5-chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or (S)-N-(5-chloropyrazin-2-yl)-2-((R)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide To a solution of 2-(4-(1H-tetrazol-5-yl)phenyl)-N-(5-chloropyrazin-2-yl)-2-(3 ,3-difluorocyclo pentyl)acetamide (Example 1.4) (249.7 mg, 0.595 mmol) in DMF (5 ml) was added triethylamine (0.083 ml, 0.595 mmol) followed by methyl iodide (0.037 ml, 0.595 mmol). The mixture was stirred at room temperature overnight. A further portion of triethylamine (0.166 ml, 0.12 mmol) and methyl iodide (0.037 ml, 0.595 mmol) was added and the mixture was stirred at room temperature for 3 hrs. The mixture was diluted with EtOAc then washed with water. The organic phase was separated using a phase separating column. The solvent was removed under vacuum and dried overnight in the vacuum oven at 40°C. The crude product was purified by chromatography on silica eluting with 0% to 30% EtOAc in iso-hexane to afford the title compound;   Example 6.3 LCMS: Rt=1.13 mins; MS m/z 434.3 [M+H]+; Method 2minLowpH Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile phase: 35% Methanol / 65% CO2 Column: Phenomenex LUX C4250 x 10 mm, 5 um @ 35degC Detection: UV @ 220 nm Flow rate: 10 ml/min Example 6.3a Diastereomer 1 of N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide Third eluted Peak: SFC Rt = 5.03 mins LCMS: Rt= 1.12mins; MS m/z 434.1 [M+H]+; Method 2minLowpH. Diastereomer 2 of N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide, SFC Rt = 3.66 mins Following removal of diastereomers 1 and 2, separation of the remaining diastereomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Mobile phase: 30% MeOH / 70% CO2 Column: Chiralpak IC, 250 x 10 mm, 5 um @ 35degC Detection: UV @ 220 nm Flow: 10 ml/min Example 6.3b Diastereomer 3 of N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide Second eluted Peak: LCMS: Rt= 1.12mins; MS m/z 434.2 [M+H]+; Method 2minLowpH. Diastereomer 4 of N-(5-Chloropyrazin-2-yl)-2-(3,3-difluorocyclopentyl)-2-(4-(2 -methyl-2H- tetrazol-5-yl)phenyl)acetamide, SFC Rt = 7.98 mins Example 6.4:   rac-2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5 -yl)phenyl)-N-(1-methyl-5- (trifluoromethyl)-1H-pyrazol-3-yl)acetamide The title compound was prepared from 2-(4-(1H-tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)- N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)acetamide by a similar method to Example 6.3; LCMS: Rt= 1.15mins; MS m/z 470.3 [M+H]+; Method 2minLowpH. Example 6.5: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(2-fluoroethyl)-2H-tetrazol- 5-yl)phenyl)acetamide To a solution of 2-(4-(1H-tetrazol-5-yl)phenyl)-N-(5-chlorothiazol-2-yl)-2-(3 ,3- difluorocyclopentyl)acetamide (Intermediate G) (100 mg, 0.235 mmol) in DMF (2 ml) was added triethylamine (0.049 ml, 0.353 mmol) followed by 1-bromo-2-fluoroethane (0.018 ml, 0.235 mmol). The mixture was stirred at room temperature for 2 hrs. A further portion of triethylamine (0.049 ml, 0.353 mmol) was added and the mixture was stirred at room temperature overnight.More triethylamine (0.049 ml, 0.353 mmol) and 1-bromo-2-fluoroethane (0.018 ml, 0.235 mmol) were added and the mixture was stirred at room temperature overnight. The mixture was diluted with DCM and washed with 1M HCl and water (4 x) then brine. The organic phase was separated using a phase separating column.   The crude product was purified by chromatography on silica eluting with a gradient of 0-50% EtOAc in iso-hexane. The product fractions were collected and solvent removed at reduced pressure and dried in an oven at 50°C over 3 days t0 afford the title compound; LCMS: Rt= 1.16mins; MS m/z 471.4 [M+H]+; Method 2minLowpH Example 6.6: rac-N-(5-Chlorothiazol-2-yl)-2-(4-(2-(cyclopropylmethyl)-2H- tetrazol-5-yl)phenyl)-2-(3,3- difluorocyclopentyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with (bromomethyl)cyclopropane; LCMS: Rt= 1.26 mins; MS m/z 479.4 [M+H]+; Method 2minLowpH Example 6.7: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(methoxymethyl)-2H- tetrazol-5-yl)phenyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with iodo(methoxy)methane;   ¹ H NMR (400 MHz, CDCl3) δ 12.23-10.30 (1H, v br s), 8.12 (2H, d), 7.40 (1H, d), 7.39 (1H, d), 7.31 (0.5H, s), 7.29 (0.5H, s) 5.89 (2H, s), 3.51 (1H, mult), 3.51 (3H, s), 3.06 (1H, mult), 2.50 (0.5H, mult), 2.30-1.31 (5.5H, complex mults)( ca.50:50 isomer ratio, hexane type solvents). Example 6.8: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(difluoromethyl)-2H- tetrazol-5-yl)phenyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with difluoroiodomethane in DMF. LCMS: Rt=1.22 mins; MS m/z 475.3[M+H]+; Method 2minLowpH ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.16-10.54 (1H, v br s), 8.18 (2H, d), 7.68 (1H, t), 7.45 (1H, d), 7.44 (1H, d), 7.32 (0.5H, s), 7.31 (0.5H, s), 3.49 (0.5H, d), 3.46 (0.5H, d), 3.07 (1H, mult), 2.53 (0.5H, mult), 2.30-1.31 (5.5H, complex overlapped mults) (50:50 isomer ratio, significant solvent residues). Example 6.9: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-isopropyl-2H-tetrazol-5- yl)phenyl)acetamide   The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with 2-iodopropane; LCMS: Rt= 1.27 mins; MS m/z 467.3[M+H]+; Method 2minLowpH Example 6.10: rac-3-(5-(4-(2-((5-Chlorothiazol-2-yl)amino)-1-(3,3-difluoro cyclopentyl)-2-oxoethyl)phenyl)- 2H-tetrazol-2-yl)propanoic acid The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with 3-iodopropanoic acid; LCMS: Rt= 1.11 mins; MS m/z 495.1[M+H]+; Method 2minLowpH Example 6.11: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(2-hydroxyethyl)-2H- tetrazol-5-yl)phenyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with 2-iodoethanol; LCMS: Rt= 1.07 mins; MS m/z 425.2 [M+H]+; Method 2minLowpH Example 6.12:   rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(1-(methoxymethyl)-1H- tetrazol-5-yl)phenyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with iodo(methoxy)methane; ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.25-10.30 (1H, v br s), 7.97 (2H, d), 7.53 (2H, d), 7.30 (0.6H, s), 7.29 (0.4H, s) 5.71 (2H, s), 3.58 (1H, mult), 3.58 (3H, s), 3.08 (1H, mult), 2.52 (0.4H, mult), 2.30- 1.31 (5.6H, complex mults) (ca 60:40 isomer ratio, also contains significant DMP solvent). Example 6.13: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-ethyl-2H-tetrazol-5- yl)phenyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with ethyl iodide; LCMS: Rt= 1.23 mins; MS m/z 453.3 [M+H]+; Method 2minLowpH Example 6.14: rac-2-(4-(2-(2-Amino-2-oxoethyl)-2H-tetrazol-5-yl)phenyl)-N- (5-chlorothiazol-2-yl)-2-(3,3- difluorocyclopentyl)acetamide   The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with 2-iodoacetamide; LCMS: Rt= 1.04 mins; MS m/z 480.3 [M+H]+; Method 2minLowpH Example 6.15: rac-N-(5-Chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(2-morpholinoethyl)-2H- tetrazol-5-yl)phenyl)acetamide The title compound was prepared by a similar method to Example 6.5 by replacing 1-bromo-2- fluoroethane with 4-(2-bromoethyl)morpholine (commercially available); LCMS: Rt= 0.93 mins; MS m/z 538.5 [M+H]+; Method 2minLowpH Example 7: rac-2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5 -yl)phenyl)-N-(3- (trifluoromethyl)isoxazol-5-yl)acetamide   Step 1: 2-(4-(1H-Tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)-N -(3-(trifluoromethyl)isoxazol- 5-yl)acetamide To a solution of 2-(4-cyanophenyl)-2-(3,3-difluorocyclopentyl)-N-(3-(trifluor omethyl)isoxazol-5- yl)acetamide (Example 1.34) (296.8 mg, 0.743 mmol) in toluene (5 ml) was added trimethylsilyl azide (432 mg, 3.72 mmol) and dibutyltin oxide (18.50 mg, 0.074 mmol). The mixture was stirred at 80°C overnight. After cooling to room temperature, the mixture was diluted with EtOAc and washed with sat. bicarbonate solution. The organic phase was separated, washed with water,brine and dried (MgSO4) and concentrated under reduced pressure. The resulting residue was triturated with DCM and the solid collected by filtration to afford the title compound; LCMS: Rt= 1.10 mins; MS m/z 443.2 [M+H]+; Method 2minLowpH Step 2: 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)-N-(3-(trifluoro methyl)isoxazol-5-yl)acetamide To a solution of 2-(4-(1H-tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)-N -(3- (trifluoromethyl)isoxazol-5-yl)acetamide (118.5 mg, 0.268 mmol) in DMF (2 ml) was added triethylamine (0.037 ml, 0.268 mmol) followed by methyl iodide (0.017 ml, 0.268 mmol). The mixture was stirred at room temperature overnight. The resulting mixture was diluted with EtOAc and washed with water. The organic phase was separated using a phase separating column. The solvent was removed under vacuum and dried overnight in the vacuum oven at 40°C. The crude product was purified by chromatography on silica eluting with 0% to 30% EtOAc in iso-   hexane. The product fraction were concentrated under reduced pressure to afford the title compound; LCMS: Rt= 1.20mins; MS m/z 457.3 [M+H]+; Method 2minLowpH Example 8 rac-N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,3-difluorocyclope ntyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide At room temperature, HATU (260 mg, 0.683 mmol) was added to a pale yellow solution of rac- 2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)acetic acid (Intermediate H) (200 mg, 0.621 mmol) and DIPEA (217 μl, 1.241 mmol) in DMF (2.0 ml and stirred for 1 hour.2- Amino-5-chloro-4-methyl-1,3-thiazole (115 mg, 0.621 mmol) was added and reaction mixutre stirred at room temperature for 18 hours. Water (40 ml) was added to the reaction mixture and a brown coloured solid precipitated. This was ultra-sonicated for 5 minutes before filtering. The brown solid was rinsed with water (30 ml), dissolved in ethyl acetate and 2N NaOH and transferred to a separating funnel. The aqueous phase was removed and organic phase washed once more with water and brine. The organic phase was dried over magnesium sulphate, filtered and the solvent evaporated to afford the title compound as stereoisomeric mixture; ¹ H NMR (400 MHz, DMSO-d6) δ 12.69 (1H, d), 8.05 (2H, d), 7.57 (2H, dd), 4.42 (3H, s), 3.79 (1H, t), 2.96 (1H, m), 2.39 - 1.10 (9H, m). LC-MS Rt 1.36mins MS m/z 453.1 [M+H] ⁺ Method 2minLowpHv01 Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter: Examples 8a and 8b: (S)-N-(5-Chloro-4-methylthiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide or (S)-N-(5-chloro-4-methylthiazol-2-yl)-2-((R)-3,3- difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl) acetamide or (R)-N-(5-chloro-   4-methylthiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide or (R)-N-(5-chloro-4-methylthiazol-2-yl)-2-((R)-3,3-difluorocyc lo pentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetamide Separation conditions: Column: Chiralpak AD, 250 x 10 mm, 5 um @ 35.2 °C Mobile phase: 27% Methanol / 75% CO2 Flow: 10 ml/min Detection: UV @ 220 nm Example 8a: Diastereomer 1 of N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,3-difluorocyclopentyl )-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide SFC Rt = 13.62 mins 1H NMR (400 MHz, DMSO-d6): δ 12.66 (1H, s), 8.05 (2H, d), 7.57 (2H, d), 4.42 (3H, s), 3.77 (1H, d), 2.94 (1H, m), 2.31 (1H, m), 2.19 (3H, s), 2.17-1.77 (3H, m), 1.54 (1H, m), 1.32 (1H, m). LC-MS Rt 1.35 mins MS m/z 453.0 [M+H] ⁺ Method 2minLowpHv01 Example 8b: Diastereomer 2 of N-(5-Chloro-4-methylthiazol-2-yl)-2-(3,3-difluorocyclopentyl )-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide SFC Rt = 15.69 mins   1H NMR (400 MHz, DMSO-d6): δ 12.70 (1H, d), 8.05 (2H, d), 7.56 (2H, dd), 4.42 (3H, s), 3.80 (1H, t), 2.97 (1H, m), 2.30 - 2.02 (3H, m), 2.20 (3H, s), 2.02-1.81 (2H, m), 1.67 (1H, m), 1.52 (1H, m). LC-MS Rt 1.36 mins MS m/z 453.0 [M+H] ⁺ Method 2minLowpHv01 The following examples were prepared by a similar method to that of Example 8, 8.0a and 8.0b by replacing 2-amino-5-chloro-4-methyl-1,3-thiazole with the appropriate amine (either commercially available or preparations described hereinafter). Example 8.1 rac-2-(3,3-Difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano[4,3 -d]thiazol-2-yl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide At room temperature, HATU (260 mg, 0.683 mmol) was added to a pale yellow solution of 2- (3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)ph enyl)acetic acid (Intermediate H) (200 mg, 0.621 mmol) and DIPEA (217 μl, 1.241 mmol) in DMF (2.0 ml). The reaction mixture was stirred at room temperature for 1 hour.4H,6H,7H-pyrano[4,3-D][1,3]thiazole-2-amine (97 mg, 0.621 mmol) was added the solution stirred at room temperature for 18 hours. Water (40 ml) was added to the reaction mixture and a cream coloured solid precipitated. This solid was filtered off and rinsed with water (30 ml) , then purified by reverse phase chromatography. The product fraction were concentrated under reduced pressure to form a thick suspension. This was basified with saturated bicarbonate and transferred to a separating funnel. The product was extracted into DCM (2 x 40 ml) and evaporated under reduced pressure to afford the title compound as stereoisomeric mixture; LC-MS Rt 1.16 mins MS m/z 461.1 [M+H] ⁺ Method 2minLowpHv01 1H NMR (400 MHz, DMSO-d6): δ 12.59 (1H, s), 8.04 (2H, d), 7.58 (2H, dd), 4.65 (2H, m), 4.42 (3H, s), 3.88 (2H, t), 3.79 (1H, t), 2.96 (1H, m), 2.63 (2H, br), 2.38-1.25 (6H, m). Separation of the stereoisomers by Supercritical Fluid Chromatography using the following conditions afforded the compounds listed hereinafter:   Examples 8.1a and 8.1b: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano [4,3-d]thiazol-2-yl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide or (S)-2-((R)-3,3-difluorocyclopentyl)-N-(6,7- dihydro-4H-pyrano[4,3-d]thiazol-2-yl)-2-(4-(2-methyl-2H-tetr azol-5-yl)phenyl)acetamide or (R)-2-((S)-3,3-difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano [4,3-d]thiazol-2-yl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide or (R)-2-((R)-3,3-difluorocyclopentyl)-N-(6,7- dihydro-4H-pyrano[4,3-d]thiazol-2-yl)-2-(4-(2-methyl-2H-tetr azol-5-yl)phenyl)acetamide. Separation conditions: Column: Chiralpak AD-H, 250 x 10 mm, 5 um @ 35.0 °C Mobile phase: 35% Isopropanol/65% CO2 Flow: 10 ml/min Detection: UV @ 220 nm Example 8.1a: Diastereomer 3 of 2-(3,3-difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano[4,3-d]t hiazol-2- yl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetamide SFC Rt = 15.07 mins 1H NMR (400 MHz, DMSO-d6): δ 12.41 (1H, m), 8.04 (2H, d), 7.58 (2H, d), 4.66 (2H, m), 4.42 (3H, s), 3.88 (2H, t), 3.81 (1H, d), 2.98 (1H, m), 2.64 (2H, m), 2.31-1.81 (4H, m), 1.66 (1H, m), 1.52 (1H, m).   LC-MS Rt 1.18 mins MS m/z 461.1 [M+H] ⁺ Method 2minLowpHv01 Example 8.1b: Diastereomer 4 of 2-(3,3-difluorocyclopentyl)-N-(6,7-dihydro-4H-pyrano[4,3-d]t hiazol-2- yl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl)acetamide SFC Rt = 17.00 mins 1H NMR (400 MHz, DMSO-d6): δ 12.39 (1H, s), 8.04 (2H, d), 7.58 (2H, d), 4.66 (2H, m), 4.42 (3H, s), 3.89 (2H, t), 3.79 (1H, d), 2.95 (1H, m), 2.64 (2H, m), 2.38-1.77 (4H, m), 1.53 (1H, m), 1.32 (1H, m). LC-MS Rt 1.18 mins MS m/z 461.1 [M+H] ⁺ Method 2minLowpHv01 Example 9: rac-N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocyclopentyl)-2-( 4-(2-(2,2,2-trifluoroethyl)-2H- tetrazol-5-yl)phenyl)acetamide To a solution of 2-(4-(1H-tetrazol-5-yl)phenyl)-N-(5-chlorothiazol-2-yl)-2-(3 ,3-difluoro cyclopentyl)acetamide (Intermediate G) (100 mg, 0.235 mmol) in DMF (2 ml) was added cesium carbonate (153 mg, 0.471 mmol). The mixture was stirred at room temperature for 10 mins then 2,2,2-trifluoroethyl trifluoromethanesulfonate (57.4 mg, 0.247 mmol) was added. After stirring at room temperature for 1 hr, the mixture was diluted with DCM and washed with 1M HCl. The organic phase was separated using a phase separating column and concentrated under reduced pressure. The crude product was purified by chromatography on silica, eluting with a gradient of 0-50% EtOAc in iso-hexane followed by a second purification with a gradient of 0-30% EtOAc in iso-hexane to afford the title compound; LCMS: Rt= 1.25 mins; MS m/z 507.4 [M+H]+; Method 2minLowpH Example 10: Methyl 4-(tert-butyl)-2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamido)thiazole-5-carboxylate   (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid (Intermediate Ha) (0.032 g, 0.1 mmol) was dissolved in DCM (1 ml) and a couple of drops of DMF added as the reaction was cooled to 0°C. Oxalyl chloride (0.018 ml, 0.200 mmol) was added and the reaction mixture stirred at 0°C for 15 mins. The resulting mixture was concentrated under reduced pressure and the residue re-dissolved in DCM (1 ml) and reduced to dryness with a rotary evaportator to ensure all the oxalyl chloride had been removed. The residue was dissolved in DCM (1 ml) and added to a vial containing pyridine (0.040 ml, 0.500 mmol) and methyl 2-amino-4-(tert-butyl)thiazole-5-carboxylate (0.021 g, 0.1 mmol) in DCM (1 ml). The vial were capped and heated at 100°C for 30mins in a Biotage Initiator 60 microwave. The resulting mixture was concentrated under reduced pressure and purified by reverse phase preparative HPLC under the following conditions to afford the title compound Column: Waters CSH C18100 x 30mm, 5um Column temperature: Ambient (room) temperature 50-98% MeCN in water (0.1% TFA) LC-MS: Rt 1.42 mins; MS m/z 519.4 [M+H]+; Method 2minLowpHv02 The following examples were prepared by a similar method to that of Example 10 by from (S)-2- ((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-y l)phenyl)acetic acid (Intermediate Ha) and the commercially available appropriate amine. Example 10.1: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- (trifluoromethyl)thiazol-2-yl)acetamide   LC-MS: Rt =1.3 mins; MS m/z 473.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.2: (S)-N-(5-Bromopyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.26 mins; MS m/z 478.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.3: (S)-N-(6-Chlorobenzo[d]thiazol-2-yl)-2-((S)-3,3-difluorocycl opentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.39 mins; MS m/z 489.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.4: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- (trifluoromethyl)pyrazin-2-yl)acetamide   LC-MS: Rt = 0.96 mins; MS m/z 475.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.5: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5,6-dihydro-4H-cyclop enta[d]thiazol-2-yl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.26 mins; MS m/z 445.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.6: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-isopropyl-1,2,4-thi adiazol-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.28 mins; MS m/z 448.3[M+H] ⁺ ; Method 2minLowpHv02 Example 10.7: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(4,5-dimethylthiazol-2 -yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide   LC-MS: Rt = 1.19 mins; MS m/z 433.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.8: tert-Butyl 2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tet razol-5- yl)phenyl)acetamido)-4-methylthiazole-5-carboxylate LC-MS: Rt = 1.4 mins; MS m/z 519.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.9: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- methylisoxazol-5-yl)acetamide LC-MS: Rt =1.16 mins; MS m/z 403.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.10: Ethyl 2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tet razol-5- yl)phenyl)acetamido)-4-(trifluoromethyl)thiazole-5-carboxyla te   LC-MS: Rt = 1.38 mins; MS m/z 545.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.11: (S)-N-(5-Chloropyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.28 mins; MS m/z 433.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.12: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-isopropylisoxazol-5 -yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide LC-MS: Rt = 1.27 mins; MS m/z 431.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.13: (S)-N-(5-Bromopyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   LC-MS: Rt = 1.3 mins; MS m/z 477.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.14: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(6-fluorobenzo[d]thiaz ol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.32 mins; MS m/z 473.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.15: (S)-N-(5-Cyanothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.21 mins; MS m/z 430.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.16: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- (trifluoromethyl)-1,2,4-thiadiazol-5-yl)acetamide   LC-MS: Rt = 1.33 mins; MS m/z 474.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.17: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-methyl-1,2,4-thiadi azol-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.16 mins; MS m/z 420.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.18: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- methylthiazol-2-yl)acetamide LC-MS: Rt = 1.18 mins; MS m/z 419.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.19: (S)-N-(5-Bromo-4-methylpyridin-2-yl)-2-((S)-3,3-difluorocycl opentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt =1.33 mins; MS m/z 491.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.20: (S)-N-(4-Bromopyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.28 mins; MS m/z 477.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.21: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(6- (trifluoromethyl)pyridin-3-yl)acetamide LC-MS: Rt = 1.28 mins; MS m/z 467.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.22: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4,5,6,7- tetrahydrobenzo[d]thiazol-2-yl)acetamide   LC-MS: Rt =1.27 mins; MS m/z 459.4[M+H] ⁺ ; Method 2minLowpHv02 Example 10.23: (S)-N-(4-Bromothiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl)- 2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.28 mins; MS m/z 483.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.24: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- propylisoxazol-5-yl)acetamide LC-MS: Rt = 1.27 mins; MS m/z 431.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.25: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- (trifluoromethyl)pyridin-2-yl)acetamide   LC-MS: Rt = 1.33 mins; MS m/z 467.3[M+H] ⁺ ; Method 2minLowpHv02 Example 10.26: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- neopentylisoxazol-5-yl)acetamide LC-MS: Rt = 1.36 mins; MS m/z 459.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.27: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-fluoropyridin-2-yl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt =1.21 mins; MS m/z 417.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.28: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-ethyl-1,2,4-thiadia zol-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt = 1.22 mins; MS m/z 434.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.29: (S)-N-(5-Bromo-1,3,4-thiadiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.24 mins; MS m/z 484.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.30: (S)-N-(5-(tert-Butyl)-1,3,4-thiadiazol-2-yl)-2-((S)-3,3-difl uorocyclopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.28 mins; MS m/z 462.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.31: (S)-N-(6-Chloropyridin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   LC-MS: Rt = 1.29 mins; MS m/z 433.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.32: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- methylbenzo[d]thiazol-2-yl)acetamide LC-MS: Rt = 1.37 mins; MS m/z 469.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.33: (S)-N-(Benzo[d]thiazol-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.3 mins; MS m/z 455.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.34: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(4-fluoropyridin-2-yl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   LC-MS: Rt = 1.21 mins; MS m/z 417.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.35: (S)-N-(5-Chloro-4-methylpyridin-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.32 mins; MS m/z 447.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.36: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-(isopropylthio)-1,3 ,4-thiadiazol-2-yl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.32 mins; MS m/z 480.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.37: (S)-N-(6-Chloropyrazin-2-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   LC-MS: Rt = 1.25 mins; MS m/z 434.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.38: (S)-N-(5-Cyclopentyl-1,3,4-thiadiazol-2-yl)-2-((S)-3,3-diflu orocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.31 mins; MS m/z 474.4[M+H] ⁺ ; Method 2minLowpHv02 Example 10.39: (S)-N-(4-Chloro-5-formylthiazol-2-yl)-2-((S)-3,3-difluorocyc lopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.25 mins; MS m/z 467.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.40: (S)-N-(5-Cyano-6-methylpyridin-2-yl)-2-((S)-3,3-difluorocycl opentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt = 1.25 mins; MS m/z 438.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.41: Methyl 5-chloro-2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-meth yl-2H-tetrazol-5- yl)phenyl)acetamido)thiazole-4-carboxylate LC-MS: Rt =1.3 mins; MS m/z 497.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.42: (S)-N-(2,6-Dichloropyridin-4-yl)-2-((S)-3,3-difluorocyclopen tyl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide LC-MS: Rt = 1.36 mins; MS m/z 467.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.43: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-ethyl-1,3,4-thiadia zol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt = 1.18 mins; MS m/z 434.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.44: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-(furan-2-yl)isoxazo l-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.25 mins; MS m/z 455.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.45: (2S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetra zol-5-yl)phenyl)-N-(6-methyl- 4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)acetamide LC-MS: Rt = 1.33 mins; MS m/z 473.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.46: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- (methylthio)-1,3,4-thiadiazol-2-yl)acetamide   LC-MS: Rt = 1.21 mins; MS m/z 452.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.47: (S)-N-(2-Chloropyridin-4-yl)-2-((S)-3,3-difluorocyclopentyl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.22 mins; MS m/z 433.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.48: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4- methylthiazol-2-yl)acetamide LC-MS: Rt = 1.18 mins; MS m/z 419.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.49: (S)-N-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-2-((S)-3,3- difluorocyclopentyl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt = 1.27 mins; MS m/z 501.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.50: (S)-N-(6-Chloroimidazo[1,2-b]pyridazin-2-yl)-2-((S)-3,3-difl uorocyclopentyl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.24 mins; MS m/z 473.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.51: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- (trifluoromethyl)oxazol-2-yl)acetamide LC-MS: Rt = 1.2 mins; MS m/z 457.3[M+H] ⁺ ; Method 2minLowpHv02 Example 10.52: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(4-methyl-5- (pyridin-3-yl)thiazol-2-yl)acetamide   LC-MS: Rt = 0.97 mins; MS m/z 496.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.53: (S)-N-(5-Cyclopropyl-1-methyl-1H-pyrazol-3-yl)-2-((S)-3,3-di fluorocyclopentyl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.17 mins; MS m/z 442.4[M+H] ⁺ ; Method 2minLowpHv02 Example 10.54: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(4-(2-hydroxypropan-2- yl)thiazol-2-yl)-2-(4-(2-methyl- 2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.15 mins; MS m/z 463.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.55: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-(methoxymethyl)isox azol-5-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt = 1.15 mins; MS m/z 433.3[M+H] ⁺ ; Method 2minLowpHv02 Example 10.56: (S)-N-(3-(tert-Butyl)-1-methyl-1H-pyrazol-5-yl)-2-((S)-3,3-d ifluorocyclopentyl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt = 1.17 mins; MS m/z 458.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.57: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5- methylpyrazin-2-yl)acetamide LC-MS: Rt = 1.13 mins; MS m/z 414.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.58: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-(furan-2-yl)-1,3,4- thiadiazol-2-yl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide   LC-MS: Rt = 1.23 mins; MS m/z 472.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.59: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(6-fluoropyridin-3-yl) -2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt = 1.17 mins; MS m/z 417.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.60: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(5,6,7,8- tetrahydro-4H-cyclohepta[d]thiazol-2-yl)acetamide LC-MS: Rt = 1.31 mins; MS m/z 473.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.61: Ethyl 2-(2-((S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H- tetrazol-5- yl)phenyl)acetamido)thiazol-4-yl)acetate   LC-MS: Rt = 1.22 mins; MS m/z 491.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.62: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(5-(methoxymethyl)-1,3 ,4-thiadiazol-2-yl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.14 mins; MS m/z 450.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.63: (S)-N-(4-Bromophenyl)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt 1.34 =mins; MS m/z 476.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.64: (S)-N-(3,4-Dichlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   LC-MS: Rt =1.4 mins; MS m/z 466.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.65: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- (trifluoromethyl)phenyl)acetamide LC-MS: Rt =1.35 mins; MS m/z 466.3[M+H] ⁺ ; Method 2minLowpHv02 Example 10.66: (S)-N-(3-Chloro-4-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide LC-MS: Rt =1.34 mins; MS m/z 450.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.67: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)-N-(3- (trifluoromethoxy)phenyl)acetamide   LC-MS: Rt =1.36 mins; MS m/z 482.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.68: (S)-N-(3-Chloro-5-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide LC-MS: Rt =1.37 mins; MS m/z 450.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.69: (S)-N-(3-Bromophenyl)-2-((S)-3,3-difluorocyclopentyl)-2-(4-( 2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt =1.34 mins; MS m/z 476.2 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.70: (S)-N-(3,5-Dichlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide   LC-MS: Rt =1.43 mins; MS m/z 466.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.71: (S)-N-(3-Chloro-2-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide LC-MS: Rt =1.31 mins; MS m/z 450.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.72: (S)-N-(3,5-Bis(trifluoromethyl)phenyl)-2-((S)-3,3-difluorocy clopentyl)-2-(4-(2-methyl-2H- tetrazol-5-yl)phenyl)acetamide LC-MS: Rt =1.45 mins; MS m/z 534.4 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.73: (S)-N-(3-Chloro-4-cyanophenyl)-2-((S)-3,3-difluorocyclopenty l)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide   LC-MS: Rt =1.31 mins; MS m/z 457.3[M+H] ⁺ ; Method 2minLowpHv02 Example 10.74: (S)-2-((S)-3,3-Difluorocyclopentyl)-N-(3-fluorophenyl)-2-(4- (2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt =1.27 mins; MS m/z 416.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.75: (S)-N-(3-Chlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2-(4- (2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt =1.33 mins; MS m/z 432.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.76: (S)-N-(5-Chloro-2-fluorophenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide   LC-MS: Rt =1.34 mins; MS m/z 450.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.77: (S)-N-(5-Chloro-2-methylphenyl)-2-((S)-3,3-difluorocyclopent yl)-2-(4-(2-methyl-2H-tetrazol- 5-yl)phenyl)acetamide LC-MS: Rt =1.32 mins; MS m/z 446.3 [M+H] ⁺ ; Method 2minLowpHv02 Example 10.78: (S)-N-(2,5-Dichlorophenyl)-2-((S)-3,3-difluorocyclopentyl)-2 -(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetamide LC-MS: Rt =1.38 mins; MS m/z 466.2 [M+H] ⁺ ; Method 2minLowpHv02 Preparation of Intermediates Intermediate A rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid   Step 1: Ethyl 2-(3,5-dicyanophenyl)acetate Commercially available 2-(3,5-dicyanophenyl)acetic acid (5.2 g, 27.9 mmol) in EtOH (100 ml) was treated with concentrated H ₂ SO ₄ conc (500 µl, 9.38 mmol) and the resulting mixture was heated at reflux for 1.5 hrs. After cooling to room temperature, the mixture was diluted with EtOAc and washed with H ₂ O, NaHCO ₃ , brine, dried (MgSO ₄ ) and concentrated under reduced pressure to afford a light brown oil which solidified on standing. Step 2: rac-Ethyl 2-(3,5-dicyanophenyl)-2-(3-oxocyclopentyl)acetate Ethyl 2-(3,5-dicyanophenyl)acetate (10 g, 46.7 mmol) was dissolved 2-MeTHF (93 mL). Cyclopent-2-enone (Sigma - Aldrich) (4.22 g, 51.3 mmol) was added followed by TBAF (1M in THF) (23.34 mL, 23.34 mmol). The reaction mixture was stirred at room temperature over night and then quenched with sat. NH ₄ Cl(aq). The resulting mixture was stirred at room temperature for 20 min and partitioned between EtOAc and water. The organic portion was separated and washed with water (3 x), brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography, eluting with iso-hexane/EtOAc to afford the rac-ethyl 2-(3,5-dicyanophenyl)-2-(3- oxocyclopentyl)acetate; LC-MS: Rt 1.05 mins; MS m/z 295.5 [M-H]-; Method 2minLowpHv01 Step 3: Ethyl 2-(3,5-dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetate rac-Ethyl 2-(3,5-dicyanophenyl)-2-(3-oxocyclopentyl)acetate (6.4 g, 21.60 mmol) and DAST (11.41 mL, 86 mmol) were combined in DCM (80 mL). The reaction mixture was heated under flow conditions at 80°C with a residence time of 60 mins. The product stream was quenched into a saturated NaHCO ₃ aqueous solution. The quenched reaction mixture was partitioned with TBME. The organic portion was washed with sat NaHCO3 (aq), water, brine, dried over magnesium sulphate, filtered and reduced in vacuo to yield crude product. The crude product was purified by silica gel column chromatography, eluting with iso-hexane/EtOAc to afford rac- ethyl 2-(3,5-dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetate; LC MS: Rt 1.25 mins; MS m/z 317.4 [M-H]-; Method 2minLowpHv01 1H NMR (400 MHz, chloroform-d) δ 7.90 (s, 3H), 4.31 – 4.09 (m, 2H), 3.50 (dd, 1H), 2.81 (m, 1H), 2.47 (m, 0.5H), 2.35 – 2.09 (m, 2H), 1.94 (m, 1H), 1.70 – 1.46 (m, 2.5H), 1.28 (t, 3H).   Step 4: rac-2-(3,5-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid rac-Ethyl 2-(3,5- dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetate (4.3g, 13.51 mmol) was dissolved in THF (100 mL). The reaction mixture was cooled to 0 °C. A solution of LiOH.H2O (2.83 g, 67.5 mmol) in H ₂ O (50 mL) was added slowly, keeping the reaction mixture temperature below 5°C. The reaction mixture was stirred at 0 °C for 10 hrs. The reaction mixture was acidified to between pH 2-4. The reaction mixture was then partitioned between EtOAc and water. The organics were washed with 0.1M HCl aq, water, brine, dried over magnesium sulphate, filtered and reduced in vacuo. The crude product was purified by silica gel column chromatography, eluting with iso- hexane/EtOAc to afforded the title compound; 1H NMR (400 MHz, DMSO-d6) δ 12.94 (s, 1H), 8.41 (m, 1H), 8.18 (m, 2H), 3.70 (d, 1H), 2.82 (m, 1H), 2.29 – 1.49 (m, 6H). Intermediate B 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid Step 1: Ethyl 2-(3,4-dicyanophenyl)acetate A pre-cooled (cardice/acetone bath), nitrogen flushed three-necked reaction vessel was charged with lithium bis(trimethylsilyl)amide solution (1M in THF, 0.802 L, 802 mmol) with stirring. Once the temperature had stabilised at ~-70°C, a solution of 4-methylphthalonitrile (57 g, 401 mmol) in diethylene glycol dimethyl ether (1L) was added slowly over 30 minutes (T < - 60°C), to give a deep red mixture which was stirred for a further 30 minutes at -70°C. A solution of ethyl chloroformate (38 mL, 401 mmol) in diethylene glycol dimethyl ether (300 mL) was added dropwise over 15 minutes (T < -60°C) to give a dark orange/brown solution. This was left to stir on the cardice/acetone bath, to slowly warm to room temperature with stirring under an atmosphere of nitrogen overnight. The reaction was quenched by pouring into 10% aqueous ammonium chloride (1L); ethyl acetate (2.5L) and water (2L) were added, and the mixture was stirred vigorously for 15 minutes before the stirring was stopped and the mixture was allowed to separate. The lower, aqueous phase was run off, to leave the dark brown organic phase. This was washed / extracted with a further 3 x 2L water to remove the bulk of the diethylene glycol dimethyl ether. The organic phase was concentrated under reduced pressure and residual diglyme was further reduced by azeotroping under reduced pressure with water (3 x 250 mL), to give 100g of dark brown oil, which slowly solidified. Ethyl 2-(3,4-dicyanophenyl)acetate was   isolated by column chromatography: [solid load (adsorbed onto 250 mL silica from DCM); RediSep 1500g silica cartridge (conditioned with isohexane); gradient elution: 30-70% EtOAc in isohexane] as a pale yellow oil LC-MS: AcqD_08052012114426: Rt 1.00 minutes; MS m/z no ionisation; 1H NMR (400MHz, CDCl3) δ 7.80 (1H, d, J = 8.1Hz), 7.78 (1H, d, J = 1.3Hz), 7.69 (1H, dd, J = 1.8Hz, 8.1Hz), 4.21 (2H, q, J = 7.1Hz), 3.76 (3H, s), 1.30 (3H, t, J = 7.1Hz). Step 2: Ethyl 2-(3,4-dicyanophenyl)-2-(3-oxocyclopentyl)acetate ( A 5L reaction vessel, with overhead stirring and under an atmosphere of nitrogen, was charged with a solution of ethyl 2-(3,4-dicyanophenyl)acetate (120 g, 560 mmol) and cyclopent-2-enone (52mL, 616 mmol) in 2-MeTHF (2.5 L). The addition TBAF.xH2O (73.2 g, 280 mmol) was accompanied by a rapid colour change to dark red. The reaction was left to stir at room temperature for three hours. The reaction mixture was quenched by pouring into a vigorously stirring aqueous solution of 5% ammonium chloride (2L). After 15 minutes, the phases were separated. The dark brown organic solution was washed consecutively with water (2 x 2L) and brine (500mL) before drying over magnesium sulfate. Filtration and concentration under reduced pressure afforded 160g of a dark red syrup. (Ethyl 2-(3,4-dicyanophenyl)-2-(3- oxocyclopentyl)acetate was isolated by column chromatography [liquid load (in solution in DCM); RediSep 1500g silica cartridge, conditioned with n-heptane; gradient elution: 0-50% EtOAc in heptane] as a waxy yellow solid. Analytical data was consistent with ethyl 2-(3,4- dicyanophenyl)-2-(3-oxocyclopentyl)acetate as a mixture of diastereomers. LCMS Rt = 0.96 minutes, MS m/z no ionisation Method 2minLowpH 1H NMR (400 MHz, Chloroform-d) δ 7.94 – 7.65 (3H, m), 4.38 – 4.02 (2H, m), 3.68 – 3.42 (1H, m), 3.01 – 2.78 (1H, m), 2.69 – 2.51 (0.5H, m), 2.51 – 1.93 (3.5H, m), 1.85 – 1.63 (1.5H, m), 1.49 – 1.36 (0.5H, m), 1.35 – 1.20 (3H, m). Step 3: Ethyl 2-(3,4-dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetate A stock solution of ethyl 2-(3,4-dicyanophenyl)-2-(3-oxocyclopentyl)acetate (284 g, 957 mmol) and (diethylamino)sulfur trifluoride (506 mL, 3.83 mol) in DCM (1900 mL) was prepared. The resulting bright orange solution was heated by continuous flow to 80°C (40mL reactor volume / 60 minutes residence time) and quenched by directing the outlet stream into a stirred suspension of sodium bicarbonate (476 g, 5670 mmol) in water (3L) plus DCM (1L). Once the last of the reaction mixture had been collected, solid sodium hydrogencarbonate was added to the quench in very small portions, until no further effervescence was seen. Stirring was stopped, and the pH of the aqueous was determined to be ~8. The layers were separated, and the aqueous solution was extracted with fresh DCM (2L). The DCM solutions were concentrated to dryness under reduced pressure, to give ~300g of a thick black viscous oil. Ethyl 2-(3,4- dicyanophenyl)-2-(3,3-difluorocyclopentyl) acetate was isolated by column chromatography [adsorbed onto silica and split into two portions, solid load; RediSep 1500g silica cartridge   (conditioned with iso-hexane); gradient elution 15-25% EtOAc in iso-hexane] as an orange syrup. Analytical data was consistent with ethyl 2-(3,4-dicyanophenyl)-2-(3,3- difluorocyclopentyl) acetate as a mixture of diastereomers: LCMS (two overlapping peaks) Rt = 1.10/1.11 minutes, MS m/z 317.4 [M-H]- Method 2minLowpH. 1H NMR (400MHz, CDCl3) δ 7.81-7.83 (2H, m), 7.73-7.76 (1H, m), 4.09-4.25 (2H, m), 3.49-3.54 (1H, m), 2.77-2.87 (1H, m), 2.42-2.49 (0.5H, m), 1.86-2.28 (3.5H, m), 1.52-1.68 (1.5H, m), 1.23- 1.44 (3.5H, m). 19F-NMR (376 MHz, CDCl3) δ -89.57 (d _AB , J _AB = 229.6Hz), -89.66 (d _AB , J _AB = 229.6Hz), -90.72 (d _AB , J _AB = 229.6Hz), -90.86 (d _AB , J _AB = 229.6Hz). Step 4: 2-(3,4-Dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid Lithium hydroxide monohydrate (66.6 g, 1588 mmol) was dissolved in water (0.648 L) and added in one portion to a solution of ethyl 2-(3,4-dicyanophenyl)-2-(3,3-difluorocyclopentyl) acetate (252.7 g, 794 mmol) in THF (2.5 L). The reaction was stirred at room temperature for twenty four hours before being acidified by the careful addition of 2M HCl (1L). The THF was removed under reduced pressure and the resulting mixture was extracted with DCM (2 x 750mL). The DCM extractions were combined and passed through a phase separator to remove residual water. TLC (silica, 35% EtOAc in hexanes) indicated some impurities present, so the crude product was adsorbed onto silica (400 mL) under reduced pressure.2-(3,4- Dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid was isolated by column chromotography [solid load; 1500g RediSep silica cartridge (conditioned with DCM); gradient elution: 0-5% methanol in DCM] as a colourless solid. Analytical data was consistent with 2-(3,4- dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid as a mixture of diastereomers: LC-MS Rt = 1.03 minutes, m/z 579.5 [2M-H]-; Method 2minLowpHv01 1H NMR (400MHz, DMSO-d6) δ 12.94 (1H, s), 8.18 – 8.08 (2H, m), 7.94 – 7.85 (1H, m), 3.78 – 3.69 (1H, m), 2.86 – 2.70 (1H, m), 2.46 – 2.30 (0.5H, m), 2.26 – 1.49 (4.5H, m), 1.47 – 1.34 (0.5H, m), 1.34 – 1.19 (0.5H, m). 19F NMR (376MHz, DMSO-d6) δ -87.40 (d _AB , J _AB = 225MHz), -88.02 (d _AB , J _AB = 225MHz), - 88.33 (d _AB , J _AB = 225MHz), -89.17 (d _AB , J _AB = 225MHz). Intermediate Ba (S)-2-(3,4-Dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)ace tic acid   Separation of the diastereomers of 2-(3,4-dicyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid (Intermediate B) was achieved over two stages (diastereomers are numbered in order of elution (1 = fastest)). Stage 1: Chiral preparative liquid chromatography: Chiralpak IC 20µm (7.65 x 39 cm); diastereomers 3 and 4 were isolated individually by isocratic elution with n-heptane / propan-2- ol / TFA (80 : 20 : 0.05); 80 mL/min; diastereomers 1 & 2 could not be separated by this method and were isolated as a mixture by isocratic elution with n-heptane/dichloromethane/2-methyl-2- butanol/TFA (70:15:10:0.05). Stage 2: Diastereomers 1 and 2 were separated and isolated as isopropylammonium salts by chiral supercritical fluid chromatography: Chiralpak AD-H (50 x ~180mm); scCO ₂ /(ethanol + 2% isopropylamine) 90:10. Diastereomer 1 was converted to the free acid by dissolving the colourless solid in methanol (500mL) and removing the isopropylamine using a strong cation exchange sorbent (Bitoage Isolute SCX-2, 99g, 0.6meq/g). The sorbent was removed by filtration and washed with fresh methanol. The filtrate was combined with the wash and the methanol was removed under reduced pressure. Diastereomer 2 was converted to the free acid by dissolving the colourless solid in a mixture of DCM (1L) and 1M HCl(aq) (500mL). The phases were separated and the lower, organic phase was washed consecutively with fresh 1M HCl(aq) (500mL) and brine (50mL). Residual water was removed from the organic phase by passing through a phase separator. The organic solution was concentrated to dryness under reduced pressure. Chiral LC analytical method: Chiralpak iC 5μm (4.6mmx 250mm); isocratic elution n-heptane / 2-prop/TFA 85:15:0.05; 1ml/min; UV detection 240nm Diastereomer 1: (R)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)ace tic acid as a crisp, colourless foamed solid (12.25g, 69% yield) . Chiral LC Rt = 10.32 minutes. LC-MS Rt = 1.09 minutes; MS m/z 245.1 [M-CO ₂ H]-, 579.3 [2M-H]-: Method 2minLowpHv01 1H NMR (400MHz, DMSO-d6) δ 12.98 (1H, br s), 8.12-8.15 (2H, m), 7.90 (1H, dd, J = 1.7, 8.2Hz), 3.74 (1H, d, J = 10.9Hz), 2.67-2.84 (1H, m), 2.32-2.44 (1H, m), 1.84-2.13 (3H, m), 1.35- 1.45 (1H, m), 1.21-1.31 (1H, m).   19F NMR (376MHz, DMSO-d6) δ -87.45 (dAB, JAB = 226Hz), -88.16 (dAB, JAB = 226Hz). Diastereomer 2: (S)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)ace tic acid as a crisp, colourless foamed solid (14.35g, 81% yield).Chiral LC Rt = 10.78 minutes. LC-MS Rt = 1.09 minutes; MS m/z 245.3 [M-CO ₂ H]-, 579.3 [2M-H]-: Method 2minLowpHv01 1H NMR (400MHz, DMSO-d6) δ 12.98 (1H, br s), 8.12-8.15 (2H, m), 7.90 (1H, dd, J = 1.7, 8.2Hz), 3.74 (1H, d, J = 10.9Hz), 2.67-2.84 (1H, m), 2.32-2.44 (1H, m), 1.84-2.13 (3H, m), 1.35- 1.45 (1H, m), 1.21-1.31 (1H, m). 19F NMR (376MHz, DMSO-d6) δ -87.45 (d _AB , J _AB = 226Hz), -88.16 (d _AB , J _AB = 226Hz). Diastereomer 3: (R)-2-(3,4-dicyanophenyl)-2-((S)-3,3-difluorocyclopentyl)ace tic acid as a colourless powdered solid (15.01g, 85%). Chiral LC Rt = 14.15 minutes. LC-MS Rt = 4.57 minutes; MS m/z 245.1 [M-CO ₂ H]-, 579.3 [2M-H]-: Method 10minLowpHv01 1H NMR (400MHz, DMSO-d6) δ 12.96 (1H, s), 8.13-8.11 (2H, m), 7.90-7.88 (1H, dd, J = 1.5, 8.2Hz), 3.74 (1H, d, J = 10.8Hz), 2.81-2.75 (1H, m), 2.22-2.03 (3H, m), 1.85-1.51 (3H, m). 19F NMR (376MHz, DMSO-d6) δ -88.03 (d _AB , J _AB = 225Hz), -89.13 (d _AB , J _AB = 225Hz). Diastereomer 4: (S)-2-(3,4-dicyanophenyl)-2-((R)-3,3-difluorocyclopentyl)ace tic acid as a colourless powdered solid (15.52g, 87%). Chiral LC Rt = 23.89 minutes LC-MS Rt = 4.26 minutes; MS m/z 245.3 [M-CO ₂ H], 579.5 [2M-H]-: Method 10minLowpHv01 1H NMR (400MHz, DMSO-d6) δ 12.96 (1H, s), 8.13-8.11 (2H, m), 7.90-7.88 (1H, dd, J = 1.5, 8.2Hz), 3.74 (1H, d, J = 10.8Hz), 2.81-2.75 (1H, m), 2.22-2.03 (3H, m), 1.85-1.51 (3H, m). 19F NMR (376MHz, DMSO-d6) δ -88.03 (d _AB , J _AB = 225Hz), -89.13 (d _AB , J _AB = 225Hz). Intermediate C rac-2-(4-Cyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid Step 1: Methyl 2-(4-cyanophenyl)acetate To a solution of 2-(4-cyanophenyl)acetic acid (2.9 g, 17.99 mmol) in MeOH (100 ml) was added dropwise sulfuric acid (1.918 ml, 36.0 mmol) and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the crude was dissolved in   water and extracted with DCM. The organic portion was separated using a phase separator and the solvent was removed under reduced pressure to afford the title compound as white needles which were dried in the oven at 40°C overnight. Step 2: Methyl 2-(4-cyanophenyl)-2-(3-oxocyclopentyl)acetate Reference: S. H. Kim et al. / Tetrahedron Letters 50 (2009) 3038-3041 Methyl 2-(4-cyanophenyl)acetate (3.2 g, 18.27 mmol) was placed into an oven dried, N ₂ flushed, roundbottom flask and dissolved in dry THF (40 ml). To this was then added cyclopent- 2-enone (1.683 ml, 20.09 mmol), followed by dropwise addition of TBAF.3H20 (2.88 g, 9.13 mmol) in THF (40ml). The mixture was stirred at 0°C for 1hr then gradually allowed to warm to room temperature and stirred overnight. The reaction was quenched by careful addition of NH4Cl and the mixture was extracted with EtOAc. The organic phase was separated and washed with water, 1M HCl, brine, dried (MgSO4) and evaporated under reduced pressure to give thte title compound as a brown oil; Step 3: Methyl 2-(4-cyanophenyl)-2-(3,3-difluorocyclopentyl)acetate Methyl 2-(4-cyanophenyl)-2-(3-oxocyclopentyl)acetate (4.77 g, 18.54 mmol) was placed into a roundbottom flask and dissolved in dry DCM (150 ml). To this was then added DAST (9.80 ml, 74.2 mmol) and the contents left stirring at room temperature for 3 days. The resulting mixture was diluted with DCM (10 ml), placed in an ice bath and MeOH (15 ml) was added carefully keeping the temperature below 10°C. Water was added and the mixture was transferred to a separating funnel. The organic portion was separated, washed with brine, dried (MgSO ₄ ) and evaporated under reduced pressure to give a brown oil. The crude product was purified by chromatography on silica, eluting with 0% to 20% EtOAc in iso-hexane. The product fractions were concentrated under reduced pressure and dried in the oven at 40°C overnight to afford the title compound. Step 4: 2-(4-Cyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid Methyl 2-(4-cyanophenyl)-2-(3,3-difluorocyclopentyl)acetate (1.79 g, 6.41 mmol) was placed into a roundbottom flask and dissolved in THF (20 ml). To this was added LiOH (0.538 g, 12.82 mmol) in water (20 ml) dropwise and the mixture was stirred at room temperature for 3 hrs. The resulting mixture was neutralised by careful addition of 1M HCl and extraction into EtOAc. The organic phase was separated and washed with water, brine, dried (MgSO ₄ ) and concentrated under reduced pressure to give the title compound; LCMS: Rt= 0.97 mins; MS m/z no mass ion [M+H]+; Method 2minLowpH Intermediate D: rac-2-(3-Cyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid   Step 1: Methyl 2-(3-cyanophenyl)acetate 2-(3-Cyanophenyl)acetic acid (2 g) was dissolved in DCM (50 mL). To this was added DMF (0.192 mL) followed by oxalyl chloride (1.2 mL).. The mixture was stirred for a period of 30 min, cooled to 0°C and treated with MeOH (5.5mL) and pyridine (3.0mL). The resulting mixture was allowed to warm to room temperature and stirred for 1-2 hours.The reaction was worked up by partitioning between DCM and water The organic portion was separted and washed with aqueous sodium bicarbonate solution, aqueous citric acid and brine, dried (sodium sulfate) and filtered and concentrated under reduced pressure to afford the title compound as a yellow oil; LCMS: Rt= 0.53 mins; MS m/z 176.1 [M+H]+;2minLC_30_v003 Step 2: Methyl 2-(3-cyanophenyl)-2-(3-oxocyclopentyl)acetate TBAF (4.08mL of a 1.0M solution in THF) was added dropwise to a solution of methyl 2-(3-cyanophenyl)acetate (1.88g) and cyclopent-2-enone (0.900mL) in THF (30mL) at room temperature under nitrogen.The reaction mixture was left to stir for a period of 2-3 hours. The mixture was was partitioned between EtOAc and water, separated, washed with brine, dried (sodium sulfate) and concentrated under reduced pressure. The resulting oil was purified by chromatography on silica eluting with hexanes/EtOAc (1.25-1.0). The product fractions were concentrated under reduced pressure to afford the title compound as a colourless viscous oil. Step 3: Methyl 2-(3-cyanophenyl)-2-(3,3-difluorocyclopentyl)acetate The title compoundwas prepared from methyl 2-(3-cyanophenyl)-2-(3-oxocyclopentyl)acetate by a similar method to Intermdiate C, step 3; LCMS: Rt = 0.93mins; MS m/z 437.2 [M+H+MeCN]+ ;Method 2minLC_30_v003 Step 4: 2-(3-Cyanophenyl)-2-(3,3-difluorocyclopentyl)acetic acid The title compoundwas prepared from methyl 2-(3-cyanophenyl)-2-(3,3-difluorocyclo pentyl)acetate by a similar method to Intermdiate C, step 4; LCMS: Rt = 0.71 mins; MS m/z 266.1 [M+H]+ ;Method 2minLC_30_v003 Intermediate E: rac-2-(4-Bromophenyl)-N-(5-chlorothiazol-2-yl)-2-(3,3-difluo rocyclopentyl)acetamide   Step 1: 2-(4-bromophenyl)-2-(3,3-difluorocyclopentyl)acetic acid The title compound was prepared from methyl 2-(4-bromophenyl)acetate and cyclopent-2- enone by an analogously method to Intermediate C, steps 2-4; LCMS:Rt= 1.13 mins; MS m/z 637.12[M+H]+; Method 2minLowpH. Step 2: 2-(4-Bromophenyl)-N-(5-chlorothiazol-2-yl)-2-(3,3-difluorocy clopentyl)acetamide To a solution of 2-(4-bromophenyl)-2-(3,3-difluorocyclopentyl)acetic acid (1.6166 g, 5.07 mmol) in DCM (40 ml) was added DMF (3.92 µl, 0.051 mmol) followed by dropwise addition of oxalyl chloride (0.488 ml, 5.57 mmol). The mixture was stirred at room temperature for 1hr. To the reaction was added 5-chlorothiazol-2-amine (2.166 g, 12.66 mmol) and pyridine (2.048 ml, 25.3 mmol) and the mixture was divided into 4 microwave vials. The mixture was heated in the microwave at 80°C for 30min.The resulting mixture was filtered and purified by chromatography on silica eluting with a gradient of 0-50% EtOAc in iso-hexane. The product fractions were concentrated under reduced pressure and dried in the oven at 50°C overnight to afford the title compound; LCMS: Rt 1.27 mins; MS m/z 437.3[M+H]+; Method 2minLowpH No further purification Intermediate F: 1-((Tetrahydro-2H-pyran-4-yl)methyl)-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H- pyrazole A stirred mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.50 g, 2.58 mmol), 4-(iodomethyl)tetrahydro-2H-pyran (0.874 g, 3.87 mmol) and cesium carbonate (2.52 g, 7.73 mmol) in acetonitrile (20 ml) was heated at 80°C. The solvent was removed and the residue was partitioned between diethyl ether and water. The organic extract was dried over   MgSO4 and the solvent removed to give a colourless oil. Chromatography on silica, eluting with EtOAc, gave the product as a colourless oil. LCMS: Rt 0.94 mins; MS m/z 292.5 [M+H]+; Method 2minLC_v003 1H NMR (400MHz, CDCl3) δ 7.83 (1H, s), 7.67 (1H, s), 4.06 (2H, d), 3.98 (2H, dd), 3.48 (2H, t), 2.20 (1H, br m), 1.51 (2H, d), 1.49 (2H, dd), 1.44 (12H, s). Intermediate G: rac-2-(4-(1H-Tetrazol-5-yl)phenyl)-N-(5-chlorothiazol-2-yl)- 2-(3,3- difluorocyclopentyl)acetamide To a solution of N-(5-chlorothiazol-2-yl)-2-(4-cyanophenyl)-2-(3,3-difluorocy clopentyl)acetamide (Example 1.2) (2.94 g, 7.70 mmol) in toluene (80 ml) was added TMSN ₃ (4.47 g, 38.5 mmol) and dibutyltin oxide (0.192 g, 0.770 mmol). The mixture was stirred at 80°C overnight.The mixture was cooled to room temperature and diluted with EtOAc and washed with sat. bicarbonate solutions. The organic phase was separated and washed with water, brine, dried (MgSO ₄ ) and concentrated under reduced pressure. The resulting solid was triturated with DCM and dried overnight in the vacuum oven at 40°C to afford the title compound; LCMS: Rt= 1.06 mins; MS m/z 425.4 [M+H]+; Method 2minLowpH Intermediate H: rac-2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5 -yl)phenyl)acetic acid

  Step 1: Methyl 2-(4-(1H-tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)ac etate The title compound was prepared analogously to Intermediate G from methyl 2-(4-cyanophenyl)-2-(3,3- difluorocyclopentyl)acetate (Intermediate C, step 3) LCMS: Rt= 1.05mins; MS m/z 323.4 [M+H]+; Method 2minLowpHv01 Step 2: Methyl 2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)acetate The title compound was prepared analogously to Example 6.3 from methyl 2-(4-(1H-tetrazol-5- yl)phenyl)-2-(3,3-difluorocyclopentyl)acetate and methyl iodide (0.355 ml, 5.68 mmol); LCMS: Rt= 1.18mins; MS m/z 337.4 [M+H]+; Method 2minLowpHv01 Step 3: 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)acetic acid The title compound was prepared analogously to Intermediate C step 4 by replacing methyl 2- (4-cyanophenyl)-2-(3,3-difluorocyclopentyl)acetate with methyl 2-(3,3-difluorocyclopentyl)-2-(4- (2-methyl-2H-tetrazol-5-yl)phenyl)acetate; LCMS: Rt =1.09 mins; MS m/z 323.3 [M+H]+; Method 2minLowpHv01. Intermediate Ha: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid Step 1: Methyl 2-(4-(2H-tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)ac etate Methyl 2-(4-cyanophenyl)-2-(3,3-difluorocyclopentyl)acetate (Intermediate C, step 3) (33.0 g, 118 mmol) was dissolved in toluene (788 mL). Trimethylsilyl azide (31.4 mL, 236 mmol) was added by syringe, followed by dibutyltin oxide (2.94 g, 11.82 mmol). The resulting mixture was   heated with stirring at 75°C overnight, to leave a clear orange solution, which turned hazy when cooling to room temperature. Residual azide was quenched in two stages: 10% aqueous sodium nitrite (179 ml, 260 mmol) was cautiously added with vigorous stirring, to give a thick emulsion. This was stirred for 30 minutes before the slow addition of 0.5M H ₂ SO ₄ (aq) (200 mL) over 30 minutes. There was none of the anticipated effervescence and pH<4. The mixture was stirred for a further 30 minutes and a thick suspension was evident in the biphasic mixture. The beige solid was isolated by filtration before washing with toluene (100 mL). The solid was partitioned between water (500 mL) and ethyl acetate (1L), producing a biphasic solution. After separation of the aqueous, the organic solution was washed with water (2 x 500 mL) and brine (250 mL) before drying over MgSO ₄ . Filtration and concentration under reduced pressure afforded a pale yellow solid. Sonication in isohexane (100 mL), filtration, washing with fresh isohexane (50 mL) and air-drying left methyl 2-(4-(2H-tetrazol-5-yl)phenyl)-2-(3,3- difluorocyclopentyl)acetate as a colourless solid (31.2g, 78% isolated yield). Analytical data was consistent with methyl 2-(4-(2H-tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)ac etate as a mixture of diastereomers: LC-MS Rt = 1.17 minutes; MS m/z 323.3 [M+H]+ Method 2minLowpHv03. 1H-NMR (400MHz, DMSO-d6) δ 8.02 (2H, d, J = 7.9 Hz), 7.57 (2H, d, J = 7.9 Hz), 3.86 – 3.68 (1H, m), 3.65 – 3.57 (3H, m), 2.92 – 2.69 (1H, m), 2.45 – 1.22 (6H, m). 19F-NMR (376MHz, DMSO-d6) δ -87.48 (d _AB , J _AB = 225 Hz), -88.08 (d _AB , J _AB = 225 Hz), -88.53 (d _AB , J _AB = 225 Hz), -89.52 (d _AB , J _AB = 225 Hz). Step 2: Methyl 2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)acetate Methyl 2-(4-(2H-tetrazol-5-yl)phenyl)-2-(3,3-difluorocyclopentyl)ac etate (31.0 g, 96 mmol) was dissolved in N,N-DMF (250 mL) with stirring under nitrogen, to give a yellow solution. Methyl iodide (9.02 mL, 144 mmol) was added in one portion, followed by potassium carbonate (19.94 g, 144 mmol). A gradual temperature rise to 30°C was noted over the first 15 minutes after the addition; after one hour, the reaction was poured into 2500 mL 5% aqueous ammonia and stirred for 15 minutes before the product was extracted into DCM (2 x 250 mL). The combined DCM extractions were passed through a phase separator to remove residual water and concentrated to dryness under reduced pressure. Methyl 2-(3,3-difluorocyclopentyl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetate was isolated by column chromatography [liquid load (solution in DCM); 750 g RediSep silica column: gradient elution 0-50% ethyl acetate in hexanes] as a colourless powdered solid Analytical data was consistent with methyl 2-(3,3- difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl) acetate as a mixture of diastereomers: LC-MS Rt = 1.34 minutes; MS m/z 337.5 [M+H] ⁺ Method 2minLowpHv03   1H-NMR F10-18: AVW07327 (400MHz, CDCl3) δ 8.16 – 8.09 (2H, m), 7.49 – 7.42 (2H, m), 4.42 (3H, s), 3.71 (3H, m), 3.53 – 3.44 (1H, m), 2.99 – 2.84 (1H, m), 2.55 – 2.43 (0.5H, m), 2.30 – 1.82 (3.5H, m), 1.72 – 1.54 (1.5H, m), 1.41 – 1.26 (m, 1H). 19F-NMR (376 MHz, CDCl3) δ -89.33 (d _AB , J _AB = 228 Hz), -89.90 (d _AB , J _AB = 228 Hz), -90.42 (d _AB , J _AB = 228 Hz), -90.67 (d _AB , J _AB = 228 Hz). Step 3: 2-(3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)acetic acid 0.62 M Lithium hydroxide in water (250 mL) was added in one portion to a colourless solution of methyl 2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl) phenyl)acetate (26.00 g, 77 mmol) in THF (250 mL) with stirring in one portion. The addition caused a colourless precipitate to form; the mixture was left to stir at room temperature overnight. The reaction was acidified by the addition of 6M HCl (30mL) before the bulk of the THF was removed under reduced pressure. The colourless precipitate in the resulting suspension was extracted into DCM (2 x 250mL). Residual water was removed from the DCM solution by passing through a phase separator before concentrating to dryness under reduced pressure gave 2-(3,3- difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5-yl)phenyl) acetic acid as a colourless powdered solid (24.15g, 92%). Analytical data was consistent with 2-(3,3-difluorocyclopentyl)-2-(4-(2- methyl-2H-tetrazol-5-yl)phenyl)acetic acid as a mixture of diastereomers: LC-MS FP Rt = 1.18 minutes; MS m/z 323.4 [M+H] ⁺ Method 2minLowpHv03 1H-NMR (400 MHz, DMSO-d6) δ 12.62 (1H, s), 8.03 (2H, d, J = 7.9 Hz), 7.52 (2H, d, J = 8.0 Hz), 4.43 (3H, s), 3.62 – 3.53 (1H, m), 2.83 – 2.69 (1H, m), 2.44 – 2.32 (0.5H, m), 2.27 – 1.63 (4H, m), 1.65 – 1.52 (0.5H, m), 1.49 – 1.41 (0.5H, m), 1.41 – 1.28 (0.5H, m). 19F-NMR FP (376 MHz, DMSO) δ -87.47 (d _AB ,J _AB = 228Hz), -88.07 (d _AB ,J _AB = 228Hz), -88.49 (d _AB ,J _AB = 228Hz), -89.51 (d _AB ,J _AB = 228Hz). Step 4: (S)-2-((S)-3,3-Difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid The separate diastereomers of 2-(3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetrazol-5- yl)phenyl)acetic acid were visualised using a single chromatographic method: Analytical chiral SFC (2 x coupled Chiralpak AD 5µm (250x10mm), scCO ₂ / propan-2-ol 90:10, column temperature 35°C, 10mL/min): diastereomer 1: Rt = 27.1 minutes; diastereomer 2: Rt = 29.5 minutes; diastereomer 3: Rt = 36.5 minutes; diastereomer 4: Rt = 38.6 minutes. The diastereomers were resolved chromatographically over three stages. Collected fractions were concentrated to dryness under reduced pressure; the residues were triturated with a mixture of DCM and hexanes, sonicated, filtered and dried, to give each diastereomer as a colourless powdered solid. Stage 1: Preparative chiral SFC [Chiralpak AD-H 5µm (250 x 30 mm); isocratic 25% MeOH in CO ₂ ; 100mL/min; column temperature 40°C; UV detection @ 220 nm] gave two peaks: Peak A: Rt = 3.5-4.5 minutes (a mixture of diastereomers 1, 2 and 3); Peak B: Rt = 5.7-6.8 minutes (diastereomer 4).   Stage 2: Preparative chiral SFC [Chiralcel AD-H 5µm (250 x 30 mm); isocratic 10% methanol in sc-CO2: 100mL/min; UV detection @ 220 nm] gave two peaks: Peak A: first eluting (a mixture of diasteromers 2 and 3); Peak B: second eluting (diastereomer 1). Stage 3: Preparative chiral SFC [2 x coupled Chiralpak AD-H 5µm (250 x 10mm); isocratic 10% propan-2-ol in sc-CO ₂ ; 10mL/min; column temperature 35°C; UV detection @ 220-260 nm] gave two peaks: Peak A: first eluting (diasteromer 2); Peak B: second eluting (diastereomer 3). Analytical data confirmed diastereomers 1 and 2 to be enantiomers of one another, as were diasteromers 3 and 4. Crystalline samples of diastereomers 2 and 3 were prepared by evaporative crystallisation from tert-butylmethyl ether; absolute configurations were obtained by single crystal X-ray diffraction. Diastereomer 1: (R)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid: Analytical chiral SFC (2 x coupled Chiralpak AD 5µm (250x10mm), scCO ₂ / propan-2-ol 90:10, column temperature 35°C, 10mL/min): Rt = 27.1 minutes; LC-MS Rt = 1.19 minutes; MS m/z 323.4 [M+H] ⁺ Method 2minLowpHv03; 1H-NMR (400 MHz, DMSO-d6) δ 12.67 (1H, s), 8.03 (2H, d, J = 7.9 Hz), 7.52 (2H, d, J = 8.0 Hz), 4.43 (3H, s), 3.57 (1H, d, J = 10.8 Hz), 2.99 - 2.63 (1H, m), 2.39 - 1.92 (3H, m), 1.89 - 1.38 (3H, m). 19F-NMR (376 MHz, DMSO-d6) δ -88.05 (d _AB , J _AB = 225 Hz), -89.49 (d _AB , J _AB = 225 Hz). [α] _D ²⁸ = -64.3 (c 0.56, methanol) Diastereomer 2: (S)-2-((R)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid: Analytical chiral SFC (2 x coupled Chiralpak AD 5µm (250x10mm), scCO ₂ / propan-2-ol 90:10, column temperature 35°C, 10mL/min): Rt = 29.5 minutes; LC-MS Rt = 1.20 minutes; MS ES+ m/z 323.4 [M+H] ⁺ Method 2minLowpHv03 1H-NMR (400 MHz, DMSO-d6) δ 12.66 (1H, s), 8.22 - 7.88 (2H, m), 7.72 - 7.34 (2H, m), 3.57 (1H, d, J = 10.8 Hz), 2.95 - 2.66 (1H, m), 2.34 - 1.96 (3H, m), 1.89 - 1.42 (3H, m). 19F-NMR (376 MHz, DMSO-d6) δ -88.06 (d _AB , J _AB = 225 Hz), -89.50 (d _AB , J _AB = 225 Hz). [α] _D ²³ = +61.7 (c = 0.5, methanol). Diasteromer 3: (R)-2-((R)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid :   Analytical chiral SFC (2 x coupled Chiralpak AD 5µm (250x10mm), scCO2 / propan-2-ol 90:10, column temperature 35°C, 10mL/min): Rt = 36.5 minutes; LC-MS Rt = 1.18 minutes; MS m/z 323.3 [M+H] ⁺ Method 2minLowpHv03 1H-NMR (400 MHz, DMSO-d6) δ 12.68 (1H, s), 8.32 - 7.84 (2H, m), 7.52 (2H, d, J = 8.2 Hz), 4.43 (3H, s), 3.56 (1H, d, J = 10.8 Hz), 2.90 - 2.61 (1H, m), 2.46 - 2.26 (1H, m), 2.21 - 1.76 (3H, m), 1.56 - 1.16 (2H, m). 19F-NMR (376 MHz, DMSO-d6) δ -87.46 (d _AB , J _AB = 225 Hz), -88.48 (d _AB , J _AB = 225 Hz) [α] _D ²³ = -64.2° (c 0.5, methanol). Intermediate Ha: Diasteromer 4: (S)-2-((S)-3,3-difluorocyclopentyl)-2-(4-(2-methyl-2H-tetraz ol-5-yl)phenyl)acetic acid: Analytical chiral SFC (2 x coupled Chiralpak AD 5µm (250x10mm), scCO ₂ / propan-2-ol 90:10, column temperature 35°C, 10mL/min): Rt = 38.6 minutes; LC-MS Rt = 3.73 minutes; MS ES+ m/z 323.2 [M-H] ⁺ : Method 8minLowpHv01; 1H-NMR (400 MHz, DMSO-d6) δ 12.64 (1H, s), 8.10 - 7.98 (2H, m), 7.57 - 7.46 (2H, m), 4.43 (3H, s), 3.56 (1H, d, J = 10.9 Hz), 2.82 - 2.67 (1H, m), 2.45 - 2.31 (1H, m), 2.20 - 1.81 (3H, m), 1.53 - 1.39 (1H, m), 1.39 - 1.27 (1H, m); 19F-NMR (376 MHz, DMSO-d6) δ -87.46 (d _AB , J _AB = 224.9 Hz), -88.48 (d _AB , J _AB = 224.9 Hz);. [α] _D ²⁴ = +66.5° (c 0.57, methanol). Intermediate I rac-2-(4-((2H-Tetrazol-2-yl)methyl)phenyl)-2-(3,3-difluorocy clopentyl)acetic acid Step 1: Methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)acetate, Methyl 2-(4-((2H-tetrazol-2- yl)methyl)phenyl)acetate Methyl 2-(4-(bromomethyl)phenyl)acetate (1 g, 4.11 mmol) was placed into a round bottom flask and dissolved in dry DMF (30 ml). To this was added 1H-tetrazole (0.45M in CH ₃ CN) (13.99 ml, 6.29 mmol) followed by potassium carbonate (0.682 g, 4.94 mmol) and the contents heated and stirred at 60°C overnight. The following day, the contents were allowed to cool to   room temperature and the solvent was removed under reduced pressure. The residue was dissolved in EtOAc/H ₂ O (50 ml). The organic layer was separated and washed with water (x2), brine (x1), dried (MgSO ₄ ) and the solvent removed under reduced pressure to give a mixture of methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)acetate and methyl 2-(4-((2H-tetrazol-1- yl)methyl)phenyl) acetate as a white solid which was used in the next step without further purification. LC-MS: Rt 0.76 & 0.83 mins; MS m/z 233.1 [M+H]+; Method 2minLowpH. Step 2: rac-Methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)-2-(3-oxocyclopentyl)a cetate, rac- Methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)-2-(3-oxocyclopentyl)a cetate A mixture of methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)acetate and methyl 2-(4-((2H-tetrazol- 1-yl)methyl)phenyl)acetate (890 mg, 3.83 mmol) was placed into a round bottom flask and dissolved in dry THF (40 ml). To this was added cyclopent-2-enone (0.353 ml, 4.22 mmol) and the contents cooled in an ice bath under N ₂ . Once cool, TBAF.3H ₂ O (605 mg, 1.916 mmol) was added and the contents left stirring at this temperature for 2 hrs. After this time, the reaction was carefully quenched by addition of sat. NH ₄ Cl solution (30 ml), and extracted with EtOAc (2 x75 ml). The organic layer was separated, combined and washed with H ₂ O (x 2), brine (x 1), dried (MgSO ₄ ) and the solvent removed under reduced pressure to give a brown oil. The crude oil was chromatographed on silica gel (40g) using the Teledyne ISCO system and eluting with a gradient of 0% to 100% EtOAc/iso-hexane. The product fractions were combined and the solvent removed under reduced pressure to give (i) rac-methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)-2-(3-oxocyclopentyl)a cetate; LC-MS: Rt 0.86 mins; MS m/z 315.3 [M+H]+; Method 2minLowpH. ¹ H NMR (400 MHz, Chloroform-d) δ 8.51 (1H, d, J = 2.8 Hz), 7.40 – 7.27 (4H, m), 5.79 (2H, d, J = 6.5 Hz), 3.65 (3H, d, J = 10.3 Hz), 3.44 (1H, dd, J = 10.6, 5.4 Hz), 2.98 – 2.79 (1H, m), 2.64 – 1.29 (m, 6H). Selective NOESY NMR experiment confirmed the compound was the N-1 regioisomer. and (ii) rac-Methyl 2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-2-(3-oxocyclopentyl)a cetate LC-MS: Rt 0.80 mins; MS m/z 315.5 [M+H]+; Method 2minLowpH. ¹ H NMR (400 MHz, Chloroform-d) δ 8.69 (1H, d, J = 2.4 Hz), 7.35 – 7.19 (4H, m), 5.57 (2H, d, J = 5.0 Hz), 3.59 (3H, d, J = 10.8 Hz), 3.41 (1H, dd, J = 10.6, 5.4 Hz), 2.82 (1H, m), 2.53 – 1.25 (m, 6H). Selective NOESY NMR experiment confirmed the compound was the N-2 regioisomer. Step 3: rac-Methyl 2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-2-(3,3-difluorocyclop entyl)acetate rac-Methyl 2-(4-((1H-tetrazol-1-yl)methyl)phenyl)-2-(3-oxocyclopentyl)a cetate (step 2i) (356 mg, 1.133 mmol) was placed into a round bottom flask and dissolved in dry DCM (15 ml). To this was added DAST (0.748 ml, 5.66 mmol) and the contents left stirring at RT for 3 days. The   contents were then cooled in an ice bath and quenched via the careful addition of MeOH (3 ml) followed by H ₂ O (10 ml). The organic layer was separated and washed with H ₂ O (x2), brine (x1), dried (MgSO4) and the solvent removed under reduced pressure to give a brown oil. The crude oil was chromatographed on silica gel (12g) using the Teledyne ISCO system and eluting with a gradient of 0% to 50% EtOAc/iso-hexane. The product fractions were combined and evaporated to give rac-methyl 2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-2-(3,3- difluorocyclopentyl)acetate as an oil. LC-MS: Rt 0.80 mins; MS m/z 337.4 [M+H]+; Method 2minLowpH30. ¹ H NMR (400 MHz, Chloroform-d) δ 8.53 (1H, s), 7.40 – 7.30 (4H, m), 5.80 (2H, s), 3.66 (3H, s), 3.41 (1H, dd, J = 11.0, 4.7 Hz), 2.83 (1H, m), 1.59 (6H, m,). Step 4: rac-2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-2-(3,3-difluorocy clopentyl)acetic acid rac-Methyl 2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-2-(3,3-difluorocyclop entyl)acetate (60 mg, 0.178 mmol) was placed into a round bottom flask and dissolved in THF (3 ml). To this was added lithium hydroxide (21.36 mg, 0.892 mmol) in water (1.200 ml) and the contents left stirring at room temperature for 48 hrs. The product mixture was neutralised by careful addition of 1M HCl and extracted into EtOAc. The organic layer was separated, and washed with H ₂ O (x 2), brine (x 1), dried (MgSO ₄ ) and concentrated under reduced pressure to give rac-2-(4-((2H- tetrazol-2-yl)methyl)phenyl)-2-(3,3-difluorocyclopentyl)acet ic acid as a pale brown solid; LC-MS: Rt 1.02 mins; MS m/z 323.3 [M+H]+; Method 2minLowpHv01. Intermediate Ia rac-2-(4-((1H-tetrazol-1-yl)methyl)phenyl)-2-(3,3-difluorocy clopentyl)acetic acid The title compound was prepared analogously to Intermediate I (steps 3 and 4) from rac-Methyl 2-(4-((2H-tetrazol-2-yl)methyl)phenyl)-2-(3-oxocyclopentyl)a cetate prepared in step 2(ii); LC-MS: Rt 0.97 mins; MS m/z 323.2 [M+H]+; Method 2minLowpHv01