NEW COMPOUNDS AND METHODS FIELD OF THE INVENTION The present invention relates to compounds of Formula (I) that may act as inhibitors of checkpoint kinase 1 (Chk1). The invention also relates to pharmaceutical compositions comprising those compounds, and to their use in the treatment of disease and conditions susceptible to Chk1 inhibition, such as cancer. BACKGROUND Chk1 is a serine/threonine kinase involved in cell cycle regulation and maintenance of DNA integrity. DNA damage can be intrinsic or induced (e.g. by genotoxic agents or ionising radiation) and results in single or double strand breaks in the DNA or stalled replication forks. After DNA damage, cell proliferation is halted at the checkpoints, allowing time for DNA repair or, if the damage is too severe, induction of apoptosis. There are four major cell cycle checkpoints which are responsible for regulating cell cycle progression: G1/S, intra-S, G2/M and spindle assembly checkpoints. Chk1 activates the intra-S, S and G2/M checkpoints and as such, forms part of a network of signal pathways called the DNA damage response (DDR) pathway. Inhibition of Chk1 kinase may result in inhibition of DNA repair and therefore it may lead to increased cell death (Dai, Y. et al Clin Cancer Res.2010, 16, 376). Cancer is a disease of aberrant cell proliferation, and defects in DNA repair pathways are common in cancer cells. Such defects can make cancer cells more dependent than healthy cells on the remaining DNA repair pathways, including the cell cycle checkpoints. For example, many cancers have defects in the tumour suppressor p53 (Ozaki, T. Cancers 2011, 3, 994) which results in loss of control of the G1/S checkpoint and increased reliance on intra-S, S and G2/M checkpoints. These cancers can have increased sensitivity to Chk1 inhibitors. Other mutations or changes in expression within the DNA repair pathways may increase sensitivity to Chk1 inhibitors. Examples include ataxia telangiectasia mutated (ATM) kinase deficiency, deficiencies in the Fanconi anaemia homologous repair pathway, and mutations that result in disruption of RAD50 signalling. Another factor that can result in increased sensitivity to Chk1 inhibition is MYC overexpression. MYC overexpression combined with Chk1 inhibition can result in synthetic lethality (Chen, H. et al Sig. Transduct. Target Ther.2018, 3, 5). The MYC oncogene is a central driver in many cancers including breast, liver and colorectal cancers (Wang, C. et al Sig. Transduct. Target Ther.2021, 6, 117). Blosser reported that cyclin E dysregulation can result in increased sensitivity to Chk1 inhibition (Blosser, W. D. et al Oncotarget 2020, 11, 216) and a E2F/G2M/SAC gene expression signature was linked to sensitivity to a Chk1 inhibitor while the expression of immunity genes was linked to resistance. Conventional chemotherapeutics, such as topoisomerase inhibitors and antimetabolites, and ionising radiation induce DNA damage which is mitigated by the DNA damage repair pathway, including Chk1. Activation of the repair pathway protects cancer cells from conventional chemo- or radio-therapy. Therefore, combined treatment of Chk1 inhibitors with chemo- or radio-therapy can overcome resistance (Neizer-Ashun, F. et al Cancer Lett.2021, 497, 202). A number of small molecule inhibitors of Chk1 have previously been described. Examples include prexasertib (Angius, G. et al Cancer Chemother. Pharmacol. 2020, 85, 9), MK-8776 (SCH900776) (Guzi, T. J. et al Mol. Cancer Ther.2011, 10, 591), CCT245737 (SRA737) (Walton, M. I. et al Oncotarget 2016, 7, 2329), GDC- 0425 (Infante, J. R. et al Clin. Cancer. Res.2017, 23, 2423), rabusertib (King, C. et al Invest. New Drugs 201432, 213), CCT244747 (Lainchbury, M. et al J. Med. Chem.2012, 55, 10229). Further Chk1 inhibitor examples have been reported in patents such as WO 201520390, WO 2021043208, WO 2021104461 and WO202119236. One area of kinase drug discovery which remains challenging is the identification of central nervous system (CNS) penetrant kinase inhibitors (Heffron, T. P. Neuro. Oncol 2018, 20, 307). A Chk1 inhibitor which crosses the blood brain barrier may have additional utility in the treatment of CNS cancers such as glioma and medulloblastoma or brain metastases. For adenosine triphosphate (ATP) competitive kinase inhibitors, hydrogen bond interaction with the kinase hinge region is usually indispensable for potent inhibition (Xing, L. et al Bioorg. Med. Chem. Lett. 2015, 23, 6520). However, for improved CNS penetration, a low hydrogen bond count is preferred. In particular, a low number of hydrogen bond donating groups favours CNS penetration (Wager, T. T. et al ACS Chem. Neurosci. 2016, 7, 767; Shi, Y. et al Bioorg. Med. Chem. Lett.2018, 28, 1981). Reducing hydrogen bond count, especially hydrogen bond donor count (for improved CNS penetration), whilst maintaining good activity through hinge binding interactions remains a challenge in the identification of kinase inhibitors, which may have scope for use in CNS disorders. Similarly, a reduced topological polar surface area (tPSA) favours CNS penetration but hydrogen bonding groups in kinase inhibitors often form key binding interactions. Thus maintaining good biological activity in kinase inhibitors with low PSA remains a challenge (Wager, T. T. et al ACS Chem. Neurosci.2016, 7, 767). A number of Chk1 inhibitors which include a pyrazole-NH-pyrazine moiety have been reported such as prexasertib (Angius, G. et al Cancer Chemother. Pharmacol. 2020, 85, 9; WO20110144126) and examples in WO2022114189, WO2021119236, CN112457306, WO2017132928, WO2015120390. Based on docking studies, the pyrazole functional group in these examples provides two hydrogen bonding interactions (donor and acceptor) to Cys87 in the kinase hinge region (Xi, J. et al 2021 Based on Computational Study, 10.21203/rs.3.rs- 509168/v1). Given the importance of hinge binding interactions, removal or weakening this key interaction would be expected to be detrimental to biological activity. In this invention, an imidazole-NH-pyrazine motif has been identified with good Chk1 activity. The reduced hydrogen bond donor capacity of this motif results in increased utility in the treatment of cancers, particularly CNS cancers. Another challenge in the field of kinase drug discovery is kinase selectivity. Most small molecule kinase inhibitors interact with multiple members of the protein kinase family (Davis, M. et al Nat. Biotechnol.2011, 29, 1046). Such ‘off target’ activity can impact biological efficacy and may drive undesired effects (Yang, X. et al J. Biomed. Inform. 2010, 43, 376), thus selective agents may provide a therapeutic benefit. Several Chk1 inhibitors have been reported to also inhibit Chk2 (e.g. examples in WO2010077758; Zabludoff, S. D. et al Mol. Cancer Ther. 2008, 7, 2955). However, selectivity over Chk2 is advantageous in overriding the S-phase checkpoint (Reader, J. C. et al J. Med. Chem.2011, 54, 8328). Ablation of Chk2 in addition to Chk1 was shown to be inferior to Chk1 ablation alone, in RNAi studies (Guzi, T. J. et al Mol. Cancer Ther.2011, 10, 591). Another family of kinase proteins of relevance to the field of Chk1 inhibitors is the ribosomal S6 kinase family (RSKs). RSKs phosphorylate Chk1 at an inhibitory site, Ser280 (Ray-David, H. et al Oncogene 2013, 32, 4480). RSK inhibitors such as SL0101 increase Chk1 kinase activity through increased phosphorylation of Chk1 Ser345. Therefore, Chk1 inhibitors with reduced RSK activity may have a biological advantage. Several Chk1 inhibitors have also been reported to inhibit RSK1 and/or RSK2 (Ditano, J. P. ACS Pharmacol. Transl. Sci. 2021, 4, 730; Walton, M. I. et al Oncotarget 2016, 7, 2329). Therefore, there is still a need for compounds that can act as Chk1 inhibitors with improved properties, which may include improved brain/CNS penetration and/or improved kinase selectivity, particularly regarding Chk2 and RSKs. In this invention, compounds containing an imidazole-NH-pyrazine motif, according to Formula (I), have been identified with suitable selectivity over Chk2 and RSK proteins. These compounds may have utility in the treatment of cancer. SUMMARY OF INVENTION It has been found that compounds of Formula (I) may act as Chk1 inhibitors and therefore may treat diseases and conditions susceptible to Chk1 inhibition, such as cancer. Further, they have certain beneficial properties leading to increased potential for use as a drug compared to known compounds. This may be due to their efficacy, solubility, selectivity profiles, safety profile and/or other notable pharmacokinetic properties. In particular, an advantage may be found in the selectivity of the compounds, particularly in relation to kinase selectivity. For example, the compounds may be selective for Chk1 inhibition over ribosomal S6 kinase (RSK) inhibition, which may lead to an improved ability to treat cancer and/or fewer side effects. Additionally, another particular advantage of the compounds may be their improved brain/CNS penetration, which may be demonstrated by their lower brain efflux compared to known compounds. This may lead to an improved ability to treat cancers relating to the brain and CNS. Consequently, the invention relates to a compound of Formula (I), (I) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, enantiomer, diastereoisomer, isotopic form, N-oxide, and/or prodrug thereof, wherein each X is independently N or CR2; each Y is independently N or CR3; 0, 1, or 2 of X and Y are N; R1 , R2 and R3 are independently selected from (a) H, halo, (C -C )alkyl, (C -C )haloal 4 1 6 1 6 kyl, (C3-C9)cycloalkyl, -OR , -NR5R6, -C(O)R7 , wherein the (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, and (C ₃ -C ₉ )cycloalkyl are optionally substituted with one or more R8; (b) 4- to 7-membered non-aromatic heterocycle optionally substituted with one or more R9; and (c) 7- to 10-membered spiro, bridged or fused heterocyclic system, each of which is optionally substituted with one or more of (C1- C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, and -NR ₂ ; R4 is selected from (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, (C ₁ -C ₆ )alkylene-NR ₂ , 4- to 6-membered non-aromatic heterocycle, and 6- to 9-membered heterocyclic spiro system, wherein the 4- to 6-membered non-aromatic heterocycle and 6- to 9-membered heterocyclic spiro system are optionally substituted with one or more of halo and (C1-C6)alkyl; R5 is selected from H, (C1-C6)alkyl, and (C1-C6)haloalkyl; R6 is selected from H, (C1-C6)alkyl, (C1-C6)haloalkyl, and 4- to 7- membered non-aromatic heterocycle, wherein the heterocycle is optionally substituted with one or more of halo and (C ₁ -C ₆ )alkyl; R7 is selected from H, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, -NR ₂ , and 4- to 7- membered non-aromatic heterocycle, wherein the heterocycle is optionally substituted with one or more of halo and (C1-C6)alkyl; R8 is selected from -NR2, and -(O)n-(4- to 7-membered non-aromatic heterocycle), wherein the 4- to 7-membered non-aromatic heterocycle is optionally substituted with one or more of halo and (C ₁ -C ₆ )alkyl; R9 is selected from halo, (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, (C ₃ -C ₆ )cycloalkyl, (C1-C6)alkoxy, -NR2, -N(R)(C1-C6)hydroxyalkyl, (C1-C6)alkylene-NR2, 4- to 6- membered non-aromatic heterocycle, and 5- to 8-membered heterocyclic spiro system, wherein the (C3-C6)cycloalkyl, 4- to 6-membered non-aromatic heterocycle, and 5- to 8-membered heterocyclic spiro system are optionally substituted with one or more of halo and (C ₁ -C ₆ )alkyl; and each R is independently selected from H, (C ₁ -C ₆ )alkyl and (C ₁ - C ₆ )haloalkyl. These compounds are compounds of the invention. In the compounds of the invention, each X is independently N or CR2 , and each Y is independently N or CR3, as long as at most two out of the four ring atoms that are X and Y are N. This means that in the compounds of the invention, 0, 1, or 2 of X and Y are N. When none of X and Y are N, then each X is CR2 , each Y is CR3. This means that the ring containing X and Y in Formula (I) is a C6-aryl, i.e. an optionally substituted phenyl. In this case, the compounds of the invention are of Formula (II). N HN N N N N (II) R2 R2 R3 R3 R1 The ring containing the X and Y atom may be an optionally substituted pyridyl. This is the case when one of the four X and Y groups is N. For instance, if one X is N and the other X is CR2 , with each Y being CR3, then the compounds of the invention are of Formula (III). Similarly, if one Y is N and the other Y is CR3, with each X being CR2 , then the compounds of the invention are of Formula (IV). N The ring containing X and Y may be a pyrazinyl, pyridazyl, or pyrimidyl. This is the case when two of the four X and Y groups are N, with the remaining groups being CR2 or CR3, as appropriate. The compounds may therefore be represented by formulae (V) to (VIII). N N N HN N HN N N N N N N (VII) N (VIII) R2 R2 N N 3 3 N N R R R1 R1 It is preferrable that in the compounds of invention that 0 or 1 of the X and Y groups are N. This means that the preferred compounds of the invention are of Formula (II), Formula (III) or Formula (IV) (most preferably Formula (II) or Formula (III)), or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, enantiomer, diastereoisomer, isotopic form, N-oxide, and/or prodrug thereof, with the remainder of the groups as herein defined. This means that the ring containing X and Y is preferably an optionally substituted phenyl or pyridinyl. This means that each Y is preferably CR3. Each R1 , R2 and R3 is independently selected from H, halo, (C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )haloalkyl, (C ₃ -C ₉ )cycloalkyl, -OR4 , -NR5R6, -C(O)R7 , 4- to 7-membered non- aromatic heterocycle, and 7- to 10-membered spiro, bridged or fused heterocyclic system. The (C1-C6)alkyl, (C1-C6)haloalkyl, and (C3-C9)cycloalkyl are optionally substituted with one or more R8. The 4- to 7-membered non-aromatic heterocycle is optionally substituted with one or more R9. The 7- to 10-membered spiro, bridged or fused heterocyclic system is optionally substituted with one or more of (C ₁ -C ₆ )alkyl, (C ₁ -C ₆ )haloalkyl, and -NR ₂ . The terms “optional” or “optionally” denotes that the subsequently described event or circumstance may, but need not, occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. The term “substituted” denotes that the group to which it refers has one or more hydrogen atoms substituted for a different group. For instance, “substituted alkyl” refers to a monovalent radical of an alkane with one or more hydrogens attached to the alkyl being replaced with another group. In view of the above, the term “optionally substituted” means that the group to which it refers may or may not be substituted, e.g. for instance, with one or more halo. The term “independently selected from” denotes that each feature is individually chosen from a list without regard to the selection of the other features. As used herein, the term “halo” denotes a halogen atom, and is preferably, F, Cl, Br or I, more preferably F or Cl. The term “(C1-C6)alkyl” denotes a linear or branched alkyl group having 1 to 6 carbon atoms, i.e.1, 2, 3, 4, 5, or 6 carbon atoms. For parts of the range “(C1- C ₆ )alkyl” all subgroups thereof are contemplated, such as (C ₁ -C ₅ )alkyl, (C ₁ - C ₄ )alkyl, (C ₁ -C ₃ )alkyl, (C ₁ -C ₂ )alkyl, (C ₁ )alkyl, (C ₂ -C ₆ )alkyl, (C ₂ -C ₅ )alkyl, (C ₂ - C ₄ )alkyl, (C ₂ -C ₃ )alkyl, (C ₂ )alkyl, (C ₃ -C ₆ )alkyl, (C ₃ -C ₅ )alkyl, (C ₃ -C ₄ )alkyl, (C ₃ )alkyl, (C4-C6)alkyl, (C4-C5)alkyl, (C4)alkyl, (C5-C6)alkyl, (C5)alkyl, and (C6)alkyl. Examples of “(C1-C6)alkyl” include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and linear or branched pentyl and hexyl. When a term denotes a range, for instance “C ₁ -C ₆ ” or “1 to 6 carbon atoms” as present in the definition of “(C ₁ -C ₆ )alkyl”, each integer is considered to be disclosed, i.e.1, 2, 3, 4, 5 and 6. The term “(C ₁ -C ₆ )haloalkyl” denotes a (C ₁ -C ₆ )alkyl group in which one or more of the hydrogen atoms are independently replaced with a halo atom, e.g. F, Cl, Br, or I, preferably F or Cl, more preferably F. Each halo-substituted carbon atom in (C1-C6)haloalkyl may be mono-, di- or, where possible, trisubstituted with an independently selected halo atom. For parts of the range “(C1-C6)haloalkyl” all subgroups thereof are contemplated, such as (C1-C5)haloalkyl, (C1-C4)haloalkyl, (C ₁ -C ₃ )haloalkyl, (C ₁ -C ₂ )haloalkyl, (C ₁ )haloalkyl, (C ₂ -C ₆ )haloalkyl, (C ₂ - C5)haloalkyl, (C2-C4)haloalkyl, (C2-C3)haloalkyl, (C2)haloalkyl, (C3-C6)haloalkyl, (C3-C5)haloalkyl, (C3-C4)haloalkyl, (C3)haloalkyl, (C4-C6)haloalkyl, (C4- C ₅ )haloalkyl, (C ₄ )haloalkyl, (C ₅ -C ₆ )haloalkyl, (C ₅ )haloalkyl, and (C ₆ )haloalkyl. Examples of “(C ₁ -C ₆ )haloalkyl” include mono-, di-, and tri-halomethyl wherein the halo atoms are independently F, Cl, Br, or I, such as -CH ₂ F, -CF ₂ H, -CF ₃ , -CH ₂ Cl, -CCl2H, -CCl3, -CHFCl, -CF2Cl, -CCl2F, mono-, di- and tri-bromomethyl, mono-, di- and tri-iodomethyl. Also included is ethyl substituted with 1, 2, 3, 4, or 5 independently selected halo atoms; n-propyl and isopropyl substituted with 1, 2, 3, 4, 5, 6 or 7 independently selected halo atoms; n-butyl, isobutyl, sec-butyl, and t-butyl substituted with 1, 2, 3, 4, 5, 6, 7, 8 or 9 independently selected halo atoms; linear or branched pentyl substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9 10, or 11 independently selected halo atoms; and linear or branched hexyl substituted with 1, 2, 3, 4, 5, 6, 7, 8, 910, 11, 12 or 13 independently selected halo atoms. The term “(C1-C3)haloalkoxy” denotes -O-(C1-C3)haloalkyl, in which “(C1- C ₃ )haloalkyl” is as defined above. For parts of the range “(C ₁ -C ₃ )haloalkoxy” all subgroups thereof are contemplated, such as (C ₁ -C ₂ )haloalkoxy, (C ₁ )haloalkoxy, (C ₂ -C ₃ )haloalkoxy, (C ₂ )haloalkoxy, and (C ₃ )haloalkoxy. The term “(C3-C9)cycloalkyl” denotes a monocyclic alkyl group having 3 to 9 carbon atoms. For parts of the range “(C3-C9)cycloalkyl“ all subgroups thereof are contemplated, such as (C ₃ -C ₉ )cycloalkyl, (C ₃ -C ₈ )cycloalkyl, (C ₃ -C ₇ )cycloalkyl, (C ₃ -C ₆ )cycloalkyl, (C ₃ -C ₅ )cycloalkyl, (C ₃ -C ₄ )cycloalkyl, (C ₃ )cycloalkyl, (C ₄ -C ₉ )cycloalkyl, (C ₄ -C ₈ )cycloalkyl, (C ₄ -C ₇ )cycloalkyl, (C ₄ -C ₆ )cycloalkyl, (C4-C5)cycloalkyl, (C4)cycloalkyl, (C5-C9)cycloalkyl, (C5-C8)cycloalkyl, (C5-C7)cycloalkyl, (C5-C6)cycloalkyl, (C5)cycloalkyl, (C6-C9)cycloalkyl, (C ₆ -C ₈ )cycloalkyl, (C ₆ -C ₇ )cycloalkyl, (C ₆ )cycloalkyl, (C ₇ -C ₉ )cycloalkyl, (C ₇ -C ₈ )cycloalkyl, (C ₇ )cycloalkyl, (C ₈ -C ₉ )cycloalkyl, (C ₈ )cycloalkyl and (C ₉ )cycloalkyl. Examples of these cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and cyclononyl. There is a feature of the invention wherein any of R1 , R2 , and R3 are selected to be a (C ₃ -C ₉ )cycloalkyl optionally substituted with one or more R8. In this case, any of R1 , R2 , and R3 preferably may be a (C3-C6)cycloalkyl optionally substituted with one or more R8; more preferably cyclopropyl or cyclobutyl, each of which is optionally substituted with -NR ₂ . The term “heteroatom” denotes O, N, or S. The term “4- to 7-membered non-aromatic heterocycle” denotes a monocyclic non-aromatic ring containing 4, 5, 6 or 7 atoms in the ring, wherein at least one of those atoms (e.g.1, 2, 3, or 4, preferably 1 or 2) is a heteroatom, e.g. O, N, or S, preferably N or O. Non-aromatic heterocycles comprising other numerical ranges of ring atoms, such as 4- to 6-members, 5- to 7-members, 4- or 5-members, and 5- or 6-members, comprise the appropriate number of atoms. Examples of 4- to 7-membered non-aromatic heterocycles include, but are not limited to, , , , NH N _NH N N NH NH NH NH NH N , ^NH , , , ^NH , , ^NH , H , NH NH O HN NH NH N NH N NH O HN , , ^NH , , HN H , H , , , O N _O N N O O O O HN O NH N O , , , ^O , , HN N ^H , H , , , NH O NH HN O O N O O NH N O , ^NH , , HN H , , ^O , ^O , H , HN HN O , and O each of which may be substituted as defined herein. Further examples contain 3 or 4 heteroatoms. Preferable examples of 4- to 7-membered non-aromatic heterocycles include the following ^NH , each of which may be substituted as described herein. The term “-(O)n-(4- to 7-membered non-aromatic heterocycle)” denotes a “4- to 7- membered non-aromatic heterocycle” as defined herein, optionally linked to the rest of the compound via an oxygen group. n can be 0 or 1. This means that when ‘n’ is 1, then the oxygen linker is present and “-(O) _n -(4- to 7-membered non- aromatic heterocycle)” is -O-(4- to 7-membered non-aromatic heterocycle). When ‘n’ is 0 the oxygen linker is not present and it refers to a “4- to 7-membered non- aromatic heterocycle”. Non-limiting examples of “-(O)n-(4- to 7-membered non- aromatic heterocycle)” when n is 0 include all of those listed above for “4- to 7- membered non-aromatic heterocycle”, each of which is optionally substituted with one or more of halo or (C ₁ -C ₆ )alkyl. Non-limiting examples of “-(O) _n -(4- to 7- membered non-aromatic heterocycle)” when n is 1 include any of the 4- to 7- membered non-aromatic heterocycles listed above, wherein the heterocycle is linked to the rest of the compound via an oxygen linker. Thus, non-limiting examples of “-(O)n-(4- to 7-membered non-aromatic heterocycle)” when n is 1 include the following , each of which is optionally substituted with one or more of halo or (C ₁ -C ₆ )alkyl. Preferably, examples of “-(O)n-(4- to 7-membered non-aromatic heterocycle)” wherein n is 1 include NH, each of which is optionally substituted with one or more of halo or (C1-C6)alkyl. The term “7- to 10-membered spiro, bridged or fused heterocyclic system” denotes a non-aromatic ring system containing 7, 8, 9 or 10 atoms in the system (i.e. the one or more rings in the system), wherein at least one of those atoms (e.g.1, 2, 3, or 4 atoms) is a heteroatom, e.g. O, N, or S, preferably N or O. those “atoms in the system” do not include any optional substituents. An “8- to 10-membered spiro or fused heterocyclic system” is the same, but wherein the non-aromatic ring system contains 8, 9 or 10 atoms in the system, and the system is a spiro group or a fused bicycle. The heterocyclic ring system may be a spiro group, i.e. a group comprising two rings joined by a common tetrahedral carbon atom. In this case, it is preferably a - to 10-membered spiro heterocyclic system, such as one selected from the , , , , , , , , , , , , N ^H , , , with further examples comprising more than one heteroatom in the spiro ring system, and/or where the point of attachment to the rest of the compound may be from any of the atoms (including the heteroatoms) in the ring. The above non- limited examples may be optionally substituted as defined herein. In particular, each of these examples may be optionally substituted with one or more of (C1- C6)alkyl, (C1-C6)haloalkyl, and -NR2. Preferable examples of a 7- to 10-membered spiro heterocyclic system include , each of which is optionally substituted with one or more of (C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )haloalkyl, and -NR ₂ . A 6- to 9-membered heterocyclic spiro system is the same as the spiro heterocycle described above, but containing 6, 7, 8 or 9 ring atoms. A 7- to 9-membered heterocyclic spiro system is the same as the spiro heterocycle described above, but containing 7, 8 or 9 ring atoms. A 5- to 8-membered heterocyclic spiro system is the same as the spiro heterocycle described above, but containing 5, 6, 7 or 8 ring atoms. A 6- to 8-membered heterocyclic spiro system is the same as the spiro heterocycle described above, but containing 5, 6, 7 or 8 ring atoms. The heterocyclic ring system may be a bridged group. This is a 7- to 10- membered bridged heterocycle that is formed from a 4- to 9-membered monocycle in which two non-adjacent atoms are linked by a 1- to 3-membered bridge (and in which the total amount of atoms in the system (excluding any substituents) is from 7 to 10). At least one of the atoms in the 7- to 10-membered bridged heterocycle is a heteroatom. Heteroatoms may be in the monocyclic ring, the bridge potion, or both the monocyclic ring and the bridge. As will be appreciated, any ring within a bridge group may be considered the “monocycle”, leaving the remaining part to be the “bridge”. In this regard, a 6-membered monocycle with a 1-membered bridge between the 1- and 4-position of the monocycle, may also be considered a 5-membered monocycle with a 2-membered bridge between the 1- and 3-position of the monocycle. Non-limiting examples of a 7- to 10-membered bridged heterocyclic system include N N N N N O O O O , HN , , , ^NH _, N, NH , N N N N N N ^N _O O N ^H O , , , N , , , , N O N N N N O N O _NH O NH , , , , , , HN , each of which is optionally substituted with one or more of (C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )haloalkyl, and -NR ₂ . Preferable examples of a 7- to 10-membered bridged heterocyclic system include NH , each of which is optionally substituted with one or more of (C1-C6)alkyl, (C1- C6)haloalkyl, and -NR2, preferably (C1-C3)alkyl and more preferably methyl. The heterocyclic ring system may be a fused bicycle. As used herein, a “fused” ring system is usually two rings, or a bicycle, that share two ring atoms, as in the fused rings exemplified below. In this case, it is preferably a 7- to 10-membered fused bicyclic heterocycle. Heteroatoms may be on either of the two rings, including the atoms shared between the two rings. Non-limiting examples of a 7- to 10-membered fused heterocyclic system include , N H N N HN N N N N , , , , , _N ^{O H O H H O} , , N N NH NH NH NH , _, ^O _and ^O , each of which is optionally substituted with one or more of (C1-C6)alkyl, (C1- C6)haloalkyl, and -NR2. Preferable examples of a 7- to 10-membered fused heterocyclic system include NH , each of which is optionally substituted with one or more of (C1-C6)alkyl, (C1- C6)haloalkyl, and -NR2. The term “(C ₁ -C ₆ )alkylene” denotes a linear or branched chain diradical of (C ₁ - C ₆ )alkyl. For parts of the range “(C ₁ -C ₆ )alkylene” all subgroups thereof are contemplated, such as (C ₁ -C ₅ )alkylene, (C ₁ -C ₄ )alkylene, (C ₁ -C ₃ )alkylene, (C ₁ - C2)alkylene, (C1)alkylene, (C2-C6)alkylene, (C2-C5)alkylene, (C2-C4)alkylene, (C2- C3)alkylene, (C2)alkylene, (C3-C6)alkylene, (C3-C5)alkylene, (C3-C4)alkylene, (C3)alkylene, (C4-C6)alkylene, (C4-C5)alkylene, (C4)alkylene, (C5-C6)alkylene, (C5)alkylene, and (C6)alkylene. Non-limiting examples of “(C1-C6)alkylene” include methylene, ethylene, n-propylene, isopropylene, n-butylene, isobutylene, sec-butylene, t-butylene, and linear or branched pentylene and hexylene. Each R in “-NR2” is independently selected from H, (C1-C6)alkyl, and (C1- C6)haloalkyl. In view of this, the term “-NR2” may be a primary, secondary or tertiary amine. As such, examples of “-NR2” include but are not limited to -NH2, , , N N N N N , , , , , N N N N , , , , H N N N NH NH N N N , , , , , , , , N N , and . Further examples include groups in which each R may independently be any linear or branched (C ₁ -C ₆ )alkyl. Any of the hydrogen atoms on the above alkyl chains may be independently substituted for a halo atom. This forms a (C ₁ -C ₆ )haloalkyl. When R is a (C1-C6)haloalkyl there can be independently 0, 1, 2 or 3 halo atoms on each carbon atom (where valency permits), provided that there is at least one halo atom present. Examples of -NR2 wherein at least one R is a (C1-C6)haloalkyl include, but are not limited to, F F , In view of the above, the term “(C1-C6)alkylene-NR2” denotes an alkylamine, in which “(C ₁ -C ₆ )alkylene” and “-NR ₂ ” are as defined herein. Preferable examples of “(C ₁ -C ₆ )alkylene-NR ₂ ” include N N ^H _, ^{NH2 NH} N N 2, _, ² _, ^H , and ^H _; more preferably and most preferably . The term “-O-(C ₁ -C ₆ )alkylene-NR ₂ ” denotes an oxy-linked “(C ₁ -C ₆ )alkylene-NR ₂ ” group, in which the “(C1-C6)alkylene-NR2” is as defined above. Preferable non- limiting examples of “-O-(C1-C6)alkylene-NR2” include and most preferably The term “(C ₁ -C ₆ )alkoxy” denotes -O-(C ₁ -C ₆ alkyl) in which the (C ₁ -C ₆ )alkyl group is as defined above. For parts of the range “(C ₁ -C ₆ )alkoxy” all subgroups thereof are contemplated, such as (C ₁ -C ₅ )alkoxy, (C ₁ -C ₄ )alkoxy, (C ₁ -C ₃ )alkoxy, (C ₁ - C2)alkoxy, (C1)alkoxy, (C2-C6)alkoxy, (C2-C5)alkoxy, (C2-C4)alkoxy, (C2-C3)alkoxy, (C2)alkoxy, (C3-C6)alkoxy, (C3-C5)alkoxy, (C3-C4)alkoxy, (C3)alkoxy, (C4-C6)alkoxy, (C4-C5)alkoxy, (C4)alkoxy, (C5-C6)alkoxy, (C5)alkoxy, and (C6)alkoxy. Non-limiting examples of “(C1-C6)alkoxy” include methoxy, ethoxy, n-propoxy, isopropoxy, n- butoxy, isobutoxy, sec-butoxy, t-butoxy and linear and branched-chain pentoxy and hexoxy. The term “(C1-C6)hydroxyalkyl” denotes a (C1-C6)alkyl group in which one or more of the hydrogen atoms are independently replaced with a hydroxy group (-OH). Each hydroxy-substituted carbon atom in (C1-C6)hydroxyalkyl may be mono-, di- or, where possible, trisubstituted with a hydroxy group. For parts of the range “(C ₁ -C ₆ )hydroxyalkyl” all subgroups thereof are contemplated, such as (C ₁ - C ₅ )hydroxyalkyl, (C ₁ -C ₄ )hydroxyalkyl, (C ₁ -C ₃ )hydroxyalkyl, (C ₁ -C ₂ )hydroxyalkyl, (C1)hydroxyalkyl, (C2-C6)hydroxyalkyl, (C2-C5)hydroxyalkyl, (C2-C4)hydroxyalkyl, (C2-C3)hydroxyalkyl, (C2)hydroxyalkyl, (C3-C6)hydroxyalkyl, (C3-C5)hydroxyalkyl, (C3-C4)hydroxyalkyl, (C3)hydroxyalkyl, (C4-C6)hydroxyalkyl, (C4-C5)hydroxyalkyl, (C ₄ )hydroxyalkyl, (C ₅ -C ₆ )hydroxyalkyl, (C ₅ )hydroxyalkyl, and (C ₆ )hydroxyalkyl. Examples of “(C ₁ -C ₆ )hydroxyalkyl” include mono-, di-, and tri-hydroxymethyl. Also included is ethyl substituted with 1, 2, 3, 4, or 5 hydroxy groups; n-propyl and isopropyl substituted with 1, 2, 3, 4, 5, 6 or 7 hydroxy groups; n-butyl, isobutyl, sec-butyl, and t-butyl substituted with 1, 2, 3, 4, 5, 6, 7, 8 or hydroxy groups; linear or branched pentyl substituted with 1, 2, 3, 4, 5, 6, 7, 8, 910, or hydroxy groups; and linear or branched hexyl substituted with 1, 2, 3, 4, 5, 6, 7, 8, 910, 11, 12 or 13 hydroxy groups. The term "-N(R)(C1-C6)hydroxyalkyl” denotes a nitrogen atom linked to the rest of the compound, wherein the nitrogen atom is substituted with an R group, and a “(C1-C6)hydroxyalkyl” as defined above. Preferably, non-limiting examples of "-N(R)(C1-C6)hydroxyalkyl” include ; and most preferably . The term "-N(H)(C1-C3)alkyl” denotes a “-NR2” group, wherein one of the R groups is H and the other is a “(C ₁ -C ₃ )alkyl” as defined above. The term "-N((C1-C3)alkyl)2” denotes a “-NR2” group, wherein each R group is independently a “(C1-C3)alkyl” as defined above. The term "-N(H)(C1-C3)haloalkyl” denotes a “-NR2” group, wherein one of the R groups is H and the other is a “(C ₁ -C ₃ )haloalkyl” as defined above. Preferably, non-limiting examples of "-N(H)(C ₁ -C ₃ )haloalkyl” include F F , and most preferably H N F F F . The term “(C ₁ -C ₃ )alkylene-N((C ₁ -C ₃ )alkyl) ₂ ” denotes an alkylamine, in which “(C ₁ - C3)alkylene” and "-N((C1-C3)alkyl)2” are as defined herein. Preferably, non-limiting examples of “(C1-C3)alkylene-N((C1-C3)alkyl)2” include , and further examples wherein the (C1-C3)alkylene is ethylene or propylene. Most preferably “(C1-C3)alkylene-N((C1-C3)alkyl)2” is N . In a preferred feature of the invention, R1 is selected from 4- to 7-membered non- aromatic heterocycle optionally substituted with one or more R9; and 7- to 10- membered spiro, bridged or fused heterocyclic system optionally substituted with one or more of (C -C )alkyl, (C -C )haloalkyl, a 9 1 6 1 6 nd -NR2. In this case, R may be selected from halo, (C1-C3)alkyl, (C1-C3)haloalkyl, (C3-C6)cycloalkyl, (C1- C ₃ )alkoxy, -NR ₂ , (C ₁ -C ₃ )alkylene-NR ₂ , 4- to 6-membered non-aromatic heterocycle, and 5- to 8-membered heterocyclic spiro system. The (C ₃ - C ₆ )cycloalkyl, 4- to 6-membered non-aromatic heterocycle, and 5- to 8-membered heterocyclic spiro system are optionally substituted with one or more of halo and (C1-C6)alkyl. Additionally, each R is independently selected from H, (C1-C6)alkyl and (C1-C6)haloalkyl. Preferably R1 is linked to the rest of the compound by a heteroatom (preferably N) in the heterocycle or heterocyclic ring system of R1. In a more preferred feature of the invention, R9 is selected from -NR2, (C1- C3)alkylene-NR2, 4- to 6-membered non-aromatic heterocycle, and 5- to 8- membered heterocyclic spiro system, wherein the 4- to 6-membered non-aromatic heterocycle and 5- to 8-membered heterocyclic spiro system are optionally substituted with one or more of halo and (C ₁ -C ₆ )alkyl. Most preferably, R9 is selected from F, methyl, methoxy, -NH ₂ , -N(H)Me, -N(H)Et, -N(H)iPr, -NMe ₂ , N H N N F N N N Et, ^NH F -N(Me) 2, , F , , O , F F, O , , , N N N N N N , , , F , , and . N More preferably, , and is optionally substituted with one or more of halo, (C ₁ -C ₃ )alkyl, (C ₁ -C ₃ )alkoxy, -NH ₂ , -N(H)(C ₁ -C ₃ )alkyl _, -N((C ₁ -C ₃ )alkyl) ₂ , -N(H)(C ₁ -C ₃ )haloalkyl, -(C ₁ -C ₃ )alkylene-N((C ₁ -C ₃ )alkyl) ₂ , ^m . Each R10 is independently selected from halo and (C ₁ -C ₃ )alkyl. m can be 0, 1, 2, or 3. This means that 0, 1, 2 or 3 carbon atoms on the ring may be substituted with R10. p can be 0, 1 or 2. This means that 0, 1 or 2 carbon atoms on the ring may be substituted with R10. In spiro systems, the tetrahedral carbon atom common to the two rings cannot be substituted with R10. Most preferably , and is optionally substituted with one or more of F, Et, N , In an alternative feature of the invention, R1 is a (C ₁ -C ₃ )alkyl, preferably methyl, optionally substituted with one or more R8. In this case, R8 may be selected from -NR2, and -(O)n-(4- to 7-membered non-aromatic heterocycle), wherein the 4- to 7-membered non-aromatic heterocycle is optionally substituted with one or more of halo and (C ₁ -C ₃ )alkyl. Additionally, n is 0 or 1, and each R is independently selected from H, (C ₁ -C ₆ )alkyl and (C ₁ -C ₆ )haloalkyl. In this feature, R1 is most preferably N , wherein each of N are optionally substituted with F. In an alternative feature of the invention, R1 is -NR5R6. In this feature, R5 is selected from H, (C ₁ -C ₆ )alkyl, and (C ₁ -C ₆ )haloalkyl, preferably H and (C ₁ -C ₆ )alkyl, more preferably H and Me. Additionally, R6 is selected from H, (C ₁ -C ₆ )alkyl, (C ₁ - C ₆ )haloalkyl, and 4- to 7-membered non-aromatic heterocycle, wherein the 4- to 7-membered non-aromatic heterocycle is optionally substituted with one or more of halo and (C1-C6)alkyl. Preferably, R6 is a 5- or 6-membered non-aromatic heterocycle optionally substituted with one or more (C1-C3)alkyl, more preferably R6 is . Most preferably R5 is H . Alternatively, R1 is -OR4 , with R4 being selected from (C1-C6)alkyl, (C1- C6)haloalkyl, (C1-C6)alkylene-NR2, 4- to 6-membered non-aromatic heterocycle, and 6- to 9-membered heterocyclic spiro system. The 4- to 6-membered non- aromatic heterocycle and 6- to 9-membered heterocyclic spiro system are optionally substituted with one or more of halo and (C ₁ -C ₆ )alkyl. In this feature of the invention, each R is independently selected from H, (C1- C6)alkyl and (C1-C6)haloalkyl, and is preferably H. More preferably, R4 is selected from (C ₁ -C ₃ )alkylene-NR ₂ , 4- or 5-membered non- aromatic heterocycle, and 7- to 9-membered heterocyclic spiro system, wherein the 4- or 5-membered non-aromatic heterocycle and 7- to 9-membered heterocyclic spiro system are optionally substituted with one or more of halo and (C1-C6)alkyl. In this case, each R is independently selected from H, (C1-C6)alkyl and (C -C )haloalkyl, preferabl 4 1 6 y each R is H. Most preferably R is , each of which is optionally substituted with halo, preferably F. In alternative feature of the invention, R1 is -C(O)R7 and R7 is selected from H, (C1-C6)alkyl, (C1-C6)haloalkyl, -NR2, and 4- to 7-membered non-aromatic heterocycle, wherein the 4- to 7-membered non-aromatic heterocycle is optionally substituted with one or more of halo and (C1-C6)alkyl, and each R is independently selected from H, (C ₁ -C ₆ )alkyl and (C ₁ -C ₆ )haloalkyl. Preferably, R7 is a 4- to 7- membered non-aromatic heterocycle, optionally substituted with one or more (C ₁ - C ₃ )alkyl. Most preferably R7 is . R2 is present in the compound when at least one of the X groups is CR2. That is, at least one of the X groups is not N. If two R2 groups are present (i.e. both X groups are CR2), then each R2 is chosen independently. In a particularly preferred embodiment, R2 is selected from H, halo, (C1-C3)alkyl, (C ₁ -C ₃ )haloalkyl, (C ₁ -C ₃ )alkoxy, (C ₁ -C ₃ )haloalkoxy (preferably -OCF ₃ ), -NR ₂ and -O(C ₁ -C ₆ )alkylene-NR ₂ (preferably -O-propylene-NH ₂ ), and R is independently selected from H, (C ₁ -C ₆ )alkyl and (C ₁ -C ₆ )haloalkyl. More preferably, R2 is selected from H, halo, (C1-C3)alkyl (preferably methyl), (C1-C3)haloalkyl (preferably -CF3), and -NR (preferably -NMe ). Even more preferably 2 2 2 R is H or halo, most preferably H or F. For the reasons se out below, it may be preferable that R2 is not (C1-C3)alkoxy, and in particular no methoxy. There is also a preference for one X to be N or CH. This means that one X can be N or CH, and the other X can be N or CR2. When one X is N or CH, compounds of the invention can be N . In this case, examples of compounds of the invention may include

N N N HN N HN N HN N N N N N N N N N N R2 N CH CH N N Y Y Y Y Y Y R ¹ , R1 , R1 N HN N N N N R2 N Y Y and R1 . Without wishing to be bound by theory, it has surprisingly been found that when one X is N or CH, the activity of the compounds is improved. This may be due to the reduced steric hindrance offered by the smaller groups in the X or R2 positions, which may allow the compounds to bind more effectively to their target, possibly leading to improved Chk1 inhibition. The compounds of the invention are tolerant to a (C1-C3)alkoxy being present in the R2 position or positions. However, the presence of those (C1-C3)alkoxy groups, and in particular the presence of a methoxy group in the R2 position, is not essential for the activity of the compounds. If fact, it may impact the inhibition of Chk1, and thus the potential to treat diseases related to Chk1, such as cancer, when compared to other compounds of the invention. That said, compounds of the invention in which one or two R2 are (C ₁ -C ₃ )alkoxy (i.e. methoxy) may still be advantageous over previously known compounds. R3 is present in the compounds of the inventio when at least one of the Y groups is CR3. That is, at least one of the Y groups is not N. If two R3 groups are present (that is, both Y groups are CR3), then each R3 is chosen independently. In a particularly preferred feature of the invention, R3 is selected from H, halo (preferably F or Cl), (C1-C6)alkyl (preferably methyl), (C1-C6)haloalkyl (preferably -CF ₃ ), -OR4; a 5- to 7-membered non-aromatic heterocycle optionally substituted with one or more R9; and a 8- to 10-membered spiro or fused heterocyclic system optionally substituted with one or more of halo and (C ₁ -C ₃ )alkyl. The 5- to 7-membered non-aromatic heterocycle is preferably selected from NH , each of which is optionally substituted with one or more R9. The 8- to 10-membered spiro or fused heterocyclic system is preferably selected from , each of which is optionally substituted with one or more of halo and (C1-C3)alkyl, preferably F or methyl. In this case, R4 is preferably selected from (C ₁ -C ₆ )alkylene-NR ₂ , a 4- to 6- membered non-aromatic heterocycle, and a 6- to 8-membered heterocyclic spiro system, wherein each of the 4- to 6-membered non-aromatic heterocycle or 6- to 8-membered heterocyclic spiro system is optionally substituted with one or more of (C ₁ -C ₃ )alkyl or halo. Preferably R4 is (C ₁ -C ₃ )alkylene-NH ₂ (more preferably propylene-NH ₂ ), wherein each of NH is optionally substituted with one or more of (C1-C3)alkyl or halo. Additionally, in this feature of the invention, R9 is selected from halo, (C1-C3)alkyl (preferably methyl), -NR ₂ , -NR((C ₁ -C ₃ )hydroxyalkyl), and (C ₁ -C ₃ )alkylene-NR ₂ (preferably methylene-NR ₂ ); and each R is independently selected from H, (C ₁ - C ₆ )alkyl and (C ₁ -C ₆ )haloalkyl, preferably H or methyl. In a feature of the invention, R1 is H or methyl, at least one Y is CR3. In this case, R3 is preferably selected from -OR4 , a 5- to 7-membered non-aromatic heterocycle optionally substituted with one or more R9; and an 8- to 10-membered spiro or fused heterocyclic system optionally substituted with one or more of halo and (C ₁ - C ₃ )alkyl. In this case, R4 may be selected from (C ₁ -C ₆ )alkylene-NR ₂ , a 4- to 6- membered non-aromatic heterocycle, and a 6- to 8-membered heterocyclic spiro system, wherein each of the 4- to 6-membered non-aromatic heterocycle or 6- to 8-membered heterocyclic spiro system is optionally substituted with one or more of (C1-C3)alkyl or halo. Additionally, R9 may be selected from halo, (C1-C3)alkyl, - NR ₂ , -NR((C ₁ -C ₃ )hydroxyalkyl), and (C ₁ -C ₃ )alkylene-NR ₂ ; and each R is independently selected from H, (C ₁ -C ₆ )alkyl and (C ₁ -C ₆ )haloalkyl. Even more preferably, R3 is , , each of which is optionally substituted with one or more halo, preferably F. Particularly advantageous compounds of the invention are ^ 5-((1-(4-(6-Methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)phenyl )-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-Chloro-4-((3-fluoropyrrolidin-1-yl)methyl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Fluoro-1-methylpiperidin-4-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-((3-fluoropyrrolidin-1-yl)methyl)-6-methox yphenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-((3-fluoropyrrolidin-1-yl)methyl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((4-Methylpiperazin-1-yl)methyl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(4-Methylpiperazin-1-yl)phenyl)-1H-imidazol-4-yl)am ino)pyrazine- 2-carbonitrile ^ 5-((1-(4-(5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl )-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(6-Methyl-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-((1-methylpiperidin-4-yl)amino)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(methyl(1-methylpiperidin-4-yl)amino)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2,4-Dimethylpiperazin-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(4-Methylpiperazin-1-yl)pyridin-2-yl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(6-(4-Methylpiperazin-1-yl)pyridin-3-yl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(6-(4-methyl-1,4-Diazepan-1-yl)pyridin-3-yl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-Fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(Methyl(1-methylpiperidin-4-yl)amino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(((4-Fluoro-1-methylpyrrolidin-3-yl)oxy)methyl)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Chloro-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-Methylpiperidin-4-yl)amino)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Ethylpiperazin-1-yl)-2-methoxyphenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-Methyl-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl )-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-2-methoxy phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2,4-Dimethylpiperazin-1-yl)-2-methoxyphenyl)-1H-im idazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)azetidin-1-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(4-Methyl-1,4-diazepan-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(5-Methyl-2,5-diazaspiro[3.4]octan-2-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(methyl((1-methylpiperidin-4-yl)methyl)am ino)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(3-(Dimethylamino)pyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(8-Methyl-2,8-diazaspiro[4.5]decan-2-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Ethyl-2-methylpiperazin-1-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-Ethylpiperidin-4-yl)amino)-2-methoxyphenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(5-Methyl-2,5-diazabicyclo[2.2.2]octan-2-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(Methyl(1-methylpiperidin-4-yl)amino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(-5-methyl-2,5-diazabicyclo[2.2.1]heptan- 2-yl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-(tert-Butyl)azetidin-3-yl)oxy)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-2-methoxyphenyl) -1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-((1-Propylazetidin-3-yl)oxy)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-Propylazetidin-3-yl)oxy)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)pyridin-2-yl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-([1,3'-Bipyrrolidin]-1'-yl)-2-methoxyphenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)pyrazin-2-yl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-(tert-Butyl)azetidin-3-yl)oxy)-2-methoxyphenyl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2-methyl-6- (trifluoromethyl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-c arbonitrile ^ 5-((1-(2-Methoxy-4-(1-methylhexahydropyrrolo[3,4-b]pyrrol-5( 1H)- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-((-4-fluoro-1-methylpyrrolidin-3-yl)oxy)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2,6-dimethylpheny l)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(3-(Dimethylamino)pyrrolidin-1-yl)-4-methylphenyl)- 1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)-6-methylpyridin- 2-yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(8-Methyl-2,8-diazaspiro[4.5]decan-2-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methyl-1,6-diazaspiro[3.3]heptan-6-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(-3-(Dimethylamino)-4-fluoropyrrolidin-1-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(6-(3-(Dimethylamino)pyrrolidin-1-yl)pyridin-3-yl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-2-fluorophenyl)- 1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2-((Dimethylamino)methyl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(-3-Methyl-3,6-diazabicyclo[3.2.0]heptan-6-yl)pheny l)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2-Methyl-2,6-diazaspiro[3.4]octan-6-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-3-(trifluorometh yl)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-2-(trifluorometh yl)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Morpholinopyrrolidin-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(-3-(Dimethylamino)-4-methylpyrrolidin-1-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(-4-(Dimethylamino)-2-methylpyrrolidin-1-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)-4-methylpyrrolidin-1-yl)phenyl)- 1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)-6-(trifluorometh yl)pyridin-2-yl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)-3-methylpyrrolidin-1-yl)phenyl)- 1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-3-fluorophenyl)- 1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-(3-methyl-3,6-diazabicyclo[3.2.0]heptan-6- yl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)pyrimidin-2-yl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-(Dimethylamino)-4-(3-(dimethylamino)pyrrolidin-1-yl )phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Bis(methyl-d3)amino)pyrrolidin-1-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(-4-(Dimethylamino)-2-methylpyrrolidin-1-yl)pyridin -2-yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(-3-(Dimethylamino)-2-methylpyrrolidin-1-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methylhexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)phe nyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Ethylamino)-4-fluoropyrrolidin-1-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Ethyl(methyl)amino)pyrrolidin-1-yl)phenyl)-1H-i midazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Ethyl(methyl)amino)pyrrolidin-1-yl)pyridin-2-yl )-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Methylhexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl)phe nyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Fluoro-4-(methylamino)pyrrolidin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-((3,3,3-Trifluoropropyl)amino)pyrrolidin-1-yl)py ridin-2-yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(Methyl(1-methylpyrrolidin-3-yl)amino)phenyl)-1H-im idazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Isopropylamino)pyrrolidin-1-yl)phenyl)-1H-imida zol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3,3,4-Trimethylpiperazin-1-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(Azetidin-1-yl)-2-methylpyrrolidin-1-yl)phenyl)- 1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(6-Methyl-1,6-diazaspiro[3.3]heptan-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methyl-1,7-diazaspiro[3.5]nonan-7-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(5-Methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phe nyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(3-(Azetidin-1-yl)pyrrolidin-1-yl)pyridin-2-yl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)-2-methoxyphenyl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)-3-methylphenyl)- 1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Methylmorpholin-2-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(2-((Dimethylamino)methyl)morpholino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(3-((2-Hydroxyethyl)(methyl)amino)pyrrolidin-1-yl)p henyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(3-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-((Dimethylamino)methyl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(6-Methyl-1,6-diazaspiro[3.4]octan-1-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(3,3-Dimethylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(3-Methylazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methyl-1,6-diazaspiro[3.4]octan-6-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(3-Fluoroazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(2-Azaspiro[3.3]heptan-2-yl)pyrrolidin-1-yl)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(3-Isopropylazetidin-1-yl)pyrrolidin-1-yl)phenyl )-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(2-Methylazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(2,2-Dimethylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 1-(4-(4-((5-Cyanopyrazin-2-yl)amino)-1H-imidazol-1-yl)phenyl )-N,N- dimethylpyrrolidin-3-amine oxide ^ 5-((1-(4-(Morpholinomethyl)phenyl)-1H-imidazol-4-yl)amino)py razine-2- carbonitrile ^ 5-((1-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-imidazol-4-yl)am ino)pyrazine- 2-carbonitrile ^ 5-((1-(4-(4-Methylpiperazine-1-carbonyl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-methyl-4-(4-Methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-([1,3'-Bipyrrolidin]-1'-yl)phenyl)-1H-imidazol-4-yl )amino)pyrazine- 2-carbonitrile ^ 5-((1-(3-(3-Aminopropoxy)phenyl)-1H-imidazol-4-yl)amino)pyra zine-2- carbonitrile ^ 5-((1-(2-(3-Aminopropoxy)-6-methoxyphenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2-Aminoethoxy)phenyl)-1H-imidazol-4-yl)amino)pyraz ine-2- carbonitrile ^ 5-((1-(3-((3-Amino-4-fluoropyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Amino-4-fluoropyrrolidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Aminopyrrolidin-1-yl)phenyl)-1H-imidazol-4-yl)am ino)pyrazine- 2-carbonitrile ^ 5-((1-(4-(7-Amino-5-azaspiro[2.4]heptan-5-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Methylamino)pyrrolidin-1-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Amino-3-methylpyrrolidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Amino-4-fluoropyrrolidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Aminomethyl)azetidin-1-yl)phenyl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Aminomethyl)-3-fluoroazetidin-1-yl)phenyl)-1H-i midazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1,6-Diazaspiro[3.3]heptan-6-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3,6-Diazabicyclo[3.2.0]heptan-3-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Ethylamino)pyrrolidin-1-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Methoxy-4-(methylamino)pyrrolidin-1-yl)phenyl)-1 H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-Fluoro-4-(methylamino)pyrrolidin-1-yl)-2-methoxy phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Amino-2-methylpyrrolidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(4-Amino-3,3-difluoropiperidin-1-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-(3-Aminopropoxy)phenyl)-1H-imidazol-4-yl)amino)pyra zine-2- carbonitrile ^ 5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2-methoxyphenyl)- 1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile) ^ 5-((1-(4-((Ethylamino)methyl)-2-methoxyphenyl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(pyrrolidin-1-ylmethyl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((4,4-Difluoropiperidin-1-yl)methyl)-2-methoxypheny l)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(morpholinomethyl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((4-Fluoropiperidin-1-yl)methyl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-((2-Methyl-2-azaspiro[3.3]heptan-6-yl)oxy)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methylazetidin-3-yl)phenyl)-1H-imidazol-4-yl)ami no)pyrazine- 2-carbonitrile ^ 5-((1-(4-(9-Methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)p henyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((2-Methyl-2-azaspiro[3.3]heptan-6-yl)oxy)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-(Diethylamino)cyclopropyl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-((2-methyl-2-azaspiro[3.3]heptan-6-yl)oxy )phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(3,3-Difluorocyclobutyl)piperazin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(Oxetan-3-yl)piperazin-1-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(2-Fluoroethyl)piperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(3,3,3-Trifluoropropyl)piperazin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Ethylpiperazin-1-yl)phenyl)-1H-imidazol-4-yl)ami no)pyrazine- 2-carbonitrile ^ 5-((1-(4-(4-Isopropylpiperazin-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, enantiomer, diastereoisomer, isotopic form, N-oxide, and/or prodrug thereof. More preferred compounds of the invention include ^ 5-((1-(4-((1R,5R)-6-Methyl-3,6-diazabicyclo[3.2.0]heptan-3-y l)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(3-Chloro-4-((3-fluoropyrrolidin-1-yl)methyl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Fluoro-1-methylpiperidin-4-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(2-Fluoro-4-((3-fluoropyrrolidin-1-yl)methyl)-6-me thoxyphenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(2-Fluoro-4-((3-fluoropyrrolidin-1-yl)methyl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((4-Methylpiperazin-1-yl)methyl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(4-Methylpiperazin-1-yl)phenyl)-1H-imidazol-4-yl)am ino)pyrazine- 2-carbonitrile ^ 5-((1-(4-((1R,4R)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-y l)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.1]heptan-2-y l)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(6-Methyl-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)phenyl)-1H-im idazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-((1-methylpiperidin-4-yl)amino)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(methyl(1-methylpiperidin-4-yl)amino)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)phenyl)-1H-im idazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(2,4-Dimethylpiperazin-1-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(4-(2,4-Dimethylpiperazin-1-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-(4-Methylpiperazin-1-yl)pyridin-2-yl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(6-(4-Methylpiperazin-1-yl)pyridin-3-yl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(6-(4-methyl-1,4-Diazepan-1-yl)pyridin-3-yl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-Fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(Methyl(1-methylpiperidin-4-yl)amino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((((3S,4S)-4-Fluoro-1-methylpyrrolidin-3-yl)oxy)met hyl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Chloro-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-Methylpiperidin-4-yl)amino)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Ethylpiperazin-1-yl)-2-methoxyphenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-Methyl-4-(4-methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl )-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(4-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-2-met hoxyphenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(4-(2,4-Dimethylpiperazin-1-yl)-2-methoxyphenyl)-1 H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Dimethylamino)azetidin-1-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(4-Methyl-1,4-diazepan-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(5-Methyl-2,5-diazaspiro[3.4]octan-2-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(3-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl )-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(methyl((1-methylpiperidin-4-yl)methyl)am ino)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(3-(3-(Dimethylamino)pyrrolidin-1-yl)phenyl)-1H-im idazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(8-Methyl-2,8-diazaspiro[4.5]decan-2-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(4-Ethyl-2-methylpiperazin-1-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-Ethylpiperidin-4-yl)amino)-2-methoxyphenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1S,4S)-5-Methyl-2,5-diazabicyclo[2.2.2]octan-2-yl )phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(Methyl(1-methylpiperidin-4-yl)amino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-((1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1] heptan-2- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-(tert-Butyl)azetidin-3-yl)oxy)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-2-methoxyphe nyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-((1-Propylazetidin-3-yl)oxy)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-Propylazetidin-3-yl)oxy)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)pyridin-2-yl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-([1,3'-Bipyrrolidin]-1'-yl)-2-methoxyphenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)pyrazin-2-yl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1-(tert-Butyl)azetidin-3-yl)oxy)-2-methoxyphenyl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2-methyl-6- (trifluoromethyl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-c arbonitrile ^ 5-((1-(2-Methoxy-4-((3aR,6aR)-1-methylhexahydropyrrolo[3,4-b ]pyrrol- 5(1H)-yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitr ile ^ 5-((1-(3-(((3R,4S)-4-fluoro-1-methylpyrrolidin-3-yl)oxy)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2,6-dimethylp henyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(3-(3-(Dimethylamino)pyrrolidin-1-yl)-4-methylphen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)-6-methylpyri din-2-yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(8-Methyl-2,8-diazaspiro[4.5]decan-2-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methyl-1,6-diazaspiro[3.3]heptan-6-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3S,4R)-3-(Dimethylamino)-4-fluoropyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3S,4S)-3-(Dimethylamino)-4-fluoropyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(6-(3-(Dimethylamino)pyrrolidin-1-yl)pyridin-3-yl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-2-fluorophen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(4-(2-((Dimethylamino)methyl)pyrrolidin-1-yl)pheny l)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1R,5S)-3-Methyl-3,6-diazabicyclo[3.2.0]heptan-6-y l)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1S,5R)-3-Methyl-3,6-diazabicyclo[3.2.0]heptan-6-y l)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2-Methyl-2,6-diazaspiro[3.4]octan-6-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-3-(trifluoro methyl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-2-(trifluoro methyl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-Morpholinopyrrolidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3R,4S)-3-(Dimethylamino)-4-methylpyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((2R,4R)-4-(Dimethylamino)-2-methylpyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((2S,4R)-4-(Dimethylamino)-2-methylpyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3R,4R)-3-(Dimethylamino)-4-methylpyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)-6-(trifluoro methyl)pyridin-2- yl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)-3-methylpyrrolidin-1-yl)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Dimethylamino)pyrrolidin-1-yl)-3-fluorophen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-((1R,5S)-3-methyl-3,6-diazabicyclo[3.2.0]h eptan-6- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Fluoro-4-((1S,5R)-3-methyl-3,6-diazabicyclo[3.2.0]h eptan-6- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Dimethylamino)pyrrolidin-1-yl)pyrimidin-2-y l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(2-(Dimethylamino)-4-(3-(dimethylamino)pyrrolidin- 1-yl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Bis(methyl-d3)amino)pyrrolidin-1-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(5-((2R,4R)-4-(Dimethylamino)-2-methylpyrrolidin-1-yl) pyridin-2-yl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((2R,3R)-3-(Dimethylamino)-2-methylpyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3aR,6aR)-1-Methylhexahydropyrrolo[3,4-b]pyrrol-5( 1H)- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3S,4R)-3-(Ethylamino)-4-fluoropyrrolidin-1-yl)phe nyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Ethyl(methyl)amino)pyrrolidin-1-yl)phenyl)- 1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Ethyl(methyl)amino)pyrrolidin-1-yl)pyridin- 2-yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3aR,6aR)-4-Methylhexahydropyrrolo[3,2-b]pyrrol-1( 2H)- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3R,4S)-3-Fluoro-4-(methylamino)pyrrolidin-1-yl)ph enyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-((3,3,3-Trifluoropropyl)amino)pyrrolidin-1-y l)pyridin-2-yl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(Methyl(1-methylpyrrolidin-3-yl)amino)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (S)-5-((1-(4-(Methyl(1-methylpyrrolidin-3-yl)amino)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Isopropylamino)pyrrolidin-1-yl)phenyl)-1H-i midazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3,3,4-Trimethylpiperazin-1-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((2R,4R)-4-(Azetidin-1-yl)-2-methylpyrrolidin-1-yl) phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(6-Methyl-1,6-diazaspiro[3.3]heptan-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methyl-1,7-diazaspiro[3.5]nonan-7-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3aR,6aS)-5-Methylhexahydropyrrolo[3,4-c]pyrrol-2( 1H)- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(5-(3-(Azetidin-1-yl)pyrrolidin-1-yl)pyridin-2-yl) -1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)-2-methoxyphe nyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)-3-methylphen yl)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Methylmorpholin-2-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(4-Methylmorpholin-2-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(3-(2-((Dimethylamino)methyl)morpholino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(3-(2-((Dimethylamino)methyl)morpholino)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(3-(3-((2-Hydroxyethyl)(methyl)amino)pyrrolidin-1-yl)p henyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(3-(3-((2-Hydroxyethyl)(methyl)amino)pyrrolidin-1-yl)p henyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(3-(3-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(3-(3-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(Azetidin-1-yl)pyrrolidin-1-yl)phenyl)-1H-imidaz ol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-((Dimethylamino)methyl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-((Dimethylamino)methyl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(6-Methyl-1,6-diazaspiro[3.4]octan-1-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(6-Methyl-1,6-diazaspiro[3.4]octan-1-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(Dimethylamino)piperidin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(3,3-Dimethylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(3,3-Dimethylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(3-Methylazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(3-Methylazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(1-Methyl-1,6-diazaspiro[3.4]octan-6-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(1-Methyl-1,6-diazaspiro[3.4]octan-6-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(3-Fluoroazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(3-Fluoroazetidin-1-yl)pyrrolidin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(2-Azaspiro[3.3]heptan-2-yl)pyrrolidin-1-yl)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(2-Azaspiro[3.3]heptan-2-yl)pyrrolidin-1-yl)phen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-(3-Isopropylazetidin-1-yl)pyrrolidin-1-yl)phenyl )-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(3-Isopropylazetidin-1-yl)pyrrolidin-1-yl)phenyl )-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(4-(3-((R)-2-Methylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Diastereomer 1) ^ 5-((1-(4-(3-((R)-2-Methylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Diastereomer 2) ^ 5-((1-(4-(3-((S)-2-Methylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Diastereomer 1) ^ 5-((1-(4-(3-((S)-2-Methylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Diastereomer 2) ^ 5-((1-(4-(3-(2,2-Dimethylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(4-(3-(2,2-Dimethylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ (R)-1-(4-(4-((5-Cyanopyrazin-2-yl)amino)-1H-imidazol-1-yl)ph enyl)-N,N- dimethylpyrrolidin-3-amine oxide ^ 5-((1-(4-(Morpholinomethyl)phenyl)-1H-imidazol-4-yl)amino)py razine-2- carbonitrile ^ 5-((1-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-imidazol-4-yl)am ino)pyrazine- 2-carbonitrile ^ 5-((1-(4-(4-Methylpiperazine-1-carbonyl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-methyl-4-(4-Methylpiperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((((3S,4R)-4-fluoro-1-Methylpyrrolidin-3-yl)oxy)met hyl)phenyl)- 1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-([1,3'-Bipyrrolidin]-1'-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(3-Aminopropoxy)phenyl)-1H-imidazol-4-yl)amino)pyra zine-2- carbonitrile ^ 5-((1-(2-(3-Aminopropoxy)-6-methoxyphenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(2-Aminoethoxy)phenyl)-1H-imidazol-4-yl)amino)pyraz ine-2- carbonitrile ^ 5-((1-(3-((3R,4S)-3-Amino-4-fluoropyrrolidin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3S,4S)-3-Amino-4-fluoropyrrolidin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-Aminopyrrolidin-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(7-Amino-5-azaspiro[2.4]heptan-5-yl)phenyl)-1H- imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Methylamino)pyrrolidin-1-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-Amino-3-methylpyrrolidin-1-yl)phenyl)-1H-imi dazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3S,4R)-3-Amino-4-fluoropyrrolidin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Aminomethyl)azetidin-1-yl)phenyl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(3-(Aminomethyl)-3-fluoroazetidin-1-yl)phenyl)-1H-i midazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1,6-Diazaspiro[3.3]heptan-6-yl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((1R,5R)-3,6-Diazabicyclo[3.2.0]heptan-3-yl)phenyl) -1H-imidazol- 4-yl)amino)pyrazine-2-carbonitrile ^ (R)-5-((1-(4-(3-(Ethylamino)pyrrolidin-1-yl)phenyl)-1H-imida zol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3R,4S)-3-Methoxy-4-(methylamino)pyrrolidin-1-yl)p henyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((3R,4S)-3-Fluoro-4-(methylamino)pyrrolidin-1-yl)-2 - methoxyphenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitril e ^ 5-((1-(4-((2R,4R)-4-Amino-2-methylpyrrolidin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-(4-Amino-3,3-difluoropiperidin-1-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 1) ^ 5-((1-(3-(4-Amino-3,3-difluoropiperidin-1-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile (Enantiomer 2) ^ 5-((1-(2-(3-Aminopropoxy)phenyl)-1H-imidazol-4-yl)amino)pyra zine-2- carbonitrile ^ (R)-5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2-methoxyphen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile) ^ 5-((1-(4-((Ethylamino)methyl)-2-methoxyphenyl)-1H-imidazol-4 - yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(pyrrolidin-1-ylmethyl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((4,4-Difluoropiperidin-1-yl)methyl)-2-methoxypheny l)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-(morpholinomethyl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((4-Fluoropiperidin-1-yl)methyl)phenyl)-1H-imidazol -4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(3-((2-Methyl-2-azaspiro[3.3]heptan-6-yl)oxy)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-Methylazetidin-3-yl)phenyl)-1H-imidazol-4-yl)ami no)pyrazine- 2-carbonitrile ^ 5-((1-(4-((1R,5S)-9-Methyl-3-oxa-7,9-diazabicyclo[3.3.1]nona n-7- yl)phenyl)-1H-imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-((2-Methyl-2-azaspiro[3.3]heptan-6-yl)oxy)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(1-(Diethylamino)cyclopropyl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(2-Methoxy-4-((2-methyl-2-azaspiro[3.3]heptan-6-yl)oxy )phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(3,3-Difluorocyclobutyl)piperazin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(Oxetan-3-yl)piperazin-1-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(2-Fluoroethyl)piperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-(3,3,3-Trifluoropropyl)piperazin-1-yl)phenyl)-1H -imidazol-4- yl)amino)pyrazine-2-carbonitrile ^ 5-((1-(4-(4-Ethylpiperazin-1-yl)phenyl)-1H-imidazol-4-yl)ami no)pyrazine- 2-carbonitrile ^ 5-((1-(4-(4-Isopropylpiperazin-1-yl)phenyl)-1H-imidazol-4- yl)amino)pyrazine-2-carbonitrile or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, enantiomer, diastereoisomer, isotopic form, N-oxide, and/or prodrug thereof. In some cases, particular stereoisomers of compounds of the invention have particularly favourable properties. For some of the compounds in the list above, enantiomers and diastereomers have been separated out into ‘Enantiomer 1’ and ‘Enantiomer 2’ or ‘Diastereomer 1’ and ‘Diastereomer 2’. It will be appreciated that one of ‘Enantiomer 1’ and ‘Enantiomer 2’ is the R-enantiomer, and the other will be the S-enantiomer. Similarly, the absolute configuration of one or more of the chiral centres in the compounds listed as ‘Diastereomer 1’ and ‘Diastereomer 2’ is known, whereas one chiral centre may be R- or S- in one diastereoisomer, and the opposite configuration in the other diastereoisomer. Details of how to prepare those enantiomers and diastereomers are set out in the examples below. In any case, the skilled person would know how to prepare and separate particular enantiomers and diastereomers of the compounds above and identify their stereochemistry using known techniques and methods of the art. The compounds of the invention may be used as such or, where appropriate, as pharmacologically acceptable salts (acid or base addition salts) thereof. The pharmacologically acceptable addition salts mentioned below are meant to comprise the therapeutically active non-toxic acid and base addition salt forms that the compounds are able to form. Compounds that have basic properties can be converted to their pharmaceutically acceptable acid addition salts by treating the base form with an appropriate acid. Exemplary acids include inorganic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulphuric acid, phosphoric acid; and organic acids such as formic acid, acetic acid, propanoic acid, hydroxyacetic acid, lactic acid, pyruvic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, benzenesulphonic acid, toluenesulphonic acid, methanesulphonic acid, trifluoroacetic acid, fumaric acid, succinic acid, malic acid, tartaric acid, citric acid, salicylic acid, p-aminosalicylic acid, pamoic acid, benzoic acid, ascorbic acid and the like. Exemplary base addition salt forms are the sodium, potassium, calcium salts, and salts with pharmaceutically acceptable amines such as, for example, ammonia, alkylamines, benzathine, and amino acids, such as, e.g. arginine and lysine. The term addition salt as used herein also comprises solvates which the compounds and salts thereof are able to form, such as, for example, hydrates, alcoholates and the like. Throughout the present disclosure, a given chemical formula or name shall also encompass all pharmaceutically acceptable salts, solvates, hydrates, tautomers, enantiomers, diastereoisomers, isotopic forms, N-oxides, and/or prodrug forms thereof. It is to be understood that the compounds of the invention include any and all hydrates and/or solvates of the compound formulae. It is appreciated that certain functional groups, such as the hydroxy, amino, and like groups form complexes and/or coordination compounds with water and/or various solvents, in the various physical forms of the compounds. Accordingly, the above formulas are to be understood to include and represent those various hydrates and/or solvates. Compounds of the invention also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone – enol pairs, amide – imidic acid pairs, lactam – lactim pairs, enamine – imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1Η- and 3H-imidazole, 1Η, 2Η- and 4Η- 1,2,4-triazole, 1Η- and 2Η- isoindole, and 1Η- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. The compounds described herein can be asymmetric (e.g. having one or more stereocenters). All stereoisomers, such as enantiomers and diastereoisomers, are intended unless otherwise indicated. The terms “diastereoisomer” and “diastereomer” are used herein interchangeably. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically active starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis- and trans-geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. In the case of the compounds which contain an asymmetric carbon atom, the invention relates to the D form, the L form, and D,L mixtures and also, where more than one asymmetric carbon atom is present, to the diastereoisomeric forms. Those compounds of the invention which contain asymmetric carbon atoms, and which as a rule accrue as racemates, can be separated into the optically active isomers in a known manner, for example using an optically active acid. However, it is also possible to use an optically active starting substance from the outset, with a corresponding optically active or diastereoisomeric compound then being obtained as the end product. The term “isotopic form” refers to the fact that compounds of the invention may include isotopically-labelled and/or isotopically-enriched forms of the compounds. The compounds of the invention herein may contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, chlorine, such as 2H, 3H, 11C, 13C, 14C, 13N, 15O, 17O, 32P, 35S, 18F, 36Cl. As used herein, deuterium labelled compounds may include ‘-d’ to show that deuterium is included, i.e. “methyl-d3” indicates the group -CD3. The term “N-oxide” denotes a compound containing the N+-O- functional group, such as in the following example. O The term ”prodrugs” refers to compounds that may be converted under physiological conditions or by solvolysis to a biologically active compound of the invention. A prodrug may be inactive when administered to a subject in need thereof, but is converted in vivo to an active compound of the invention. Prodrugs are typically rapidly transformed in vivo to yield the parent compound of the invention, e.g. by hydrolysis in the blood. The prodrug compound usually offers advantages of solubility, tissue compatibility or delayed release in a mammalian organism (see Silverman, R. B., The Organic Chemistry of Drug Design and Drug Action, 2nd Ed., Elsevier Academic Press (2004), page 498 to 549). Prodrugs of a compound of the invention may be prepared by modifying functional groups, such as a hydroxy, amino or mercapto groups, present in a compound of the invention in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound of the invention. Examples of prodrugs include, but are not limited to, acetate, formate and succinate derivatives of hydroxy functional groups or phenyl carbamate derivatives of amino functional groups. For clinical use, the compounds disclosed herein are formulated into pharmaceutical compositions (or formulations) for various modes of administration. It will be appreciated that compounds of the invention may be administered together with a physiologically acceptable carrier, excipient, and/or diluent (i.e. one, two, or all three of these). The pharmaceutical compositions disclosed herein may be administered by any suitable route, preferably by oral, rectal, nasal, topical (including buccal and sublingual), sublingual, transdermal, intrathecal, transmucosal or parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration. Other formulations may conveniently be presented in unit dosage form, e.g., tablets and sustained release capsules, and in liposomes, and may be prepared by any methods well known in the art of pharmacy. Pharmaceutical formulations are usually prepared by mixing the active substance, or a pharmaceutically acceptable salt thereof, with conventional pharmaceutically acceptable carriers, diluents or excipients. Examples of excipients are water, gelatin, gum arabicum, lactose, microcrystalline cellulose, starch, sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talcum, colloidal silicon dioxide, and the like. Such formulations may also contain other pharmacologically active agents, and conventional additives, such as stabilizers, wetting agents, emulsifiers, flavouring agents, buffers, and the like. Usually, the amount of active compounds is between 0.1-95% by weight of the preparation, preferably between 0.2-20% by weight in preparations for parenteral use and more preferably between 1-50% by weight in preparations for oral administration. The formulations can be further prepared by known methods such as granulation, compression, microencapsulation, spray coating, etc. The formulations may be prepared by conventional methods in the dosage form of tablets, capsules, granules, powders, syrups, suspensions, suppositories or injections. Liquid formulations may be prepared by dissolving or suspending the active substance in water or other suitable vehicles. Tablets and granules may be coated in a conventional manner. To maintain therapeutically effective plasma concentrations for extended periods of time, compounds disclosed herein may be incorporated into slow-release formulations. The dose level and frequency of dosage of the specific compound will vary depending on a variety of factors including the potency of the specific compound employed, the metabolic stability and length of action of that compound, the patient’s age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the condition to be treated, and the patient undergoing therapy. The daily dosage may, for example, range from about 0.001 mg to about 100 mg per kilo of body weight, administered singly or multiply in doses, e.g. from about 0.01 mg to about 25 mg each. Normally, such a dosage is given orally but parenteral administration may also be chosen. An object of the present invention relates to the compounds of the invention for use as a medicament. The term ‘medicament’ denotes a substance used for medical treatment or as a medicine. The compounds of the invention may be useful as inhibitors of Chk1. As such, they are useful in the treatment or prevention of medical conditions (conditions or diseases) that are affected by Chk1. Therefore, there is provided a method of treating a disease or condition responsive to Chk1 inhibition, such as cancer, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of the invention. The compounds of the invention may be for use in medicine. This use may be in the treatment of cancer. The compounds of the invention may also be useful in the manufacture of a medicament. That medicament may be of use in the treatment of cancer. The compounds of the invention may be useful in the treatment of a range of cancers, particularly those that are susceptible to Chk1 inhibition. Non-limiting cancers include CNS cancer (including glioblastoma multiforme, glioma, neuroblastoma, medulloblastoma, DIPG and secondary brain tumours such as brain metastasis), sarcoma (including osterosarcoma, rhabdomyosarcoma, Kaposi’s sarcoma, leiomyosarcoma), ovarian cancer (including high grade serous ovarian cancer), lung cancer (including small cell lung cancer, non-small cell lung cancer), breast cancer, endometrial cancer, prostate cancer, pancreatic cancer, renal cell carcinoma, colorectal cancer (including colon cancer, rectal cancer, anal cancer), gastrointestinal cancer (including gastric cancer), thyroid cancer, bladder cancer, kidney cancer, melanoma, squamous cancer (including squamous cell carcinoma head and neck), leukemia or lymphoma. Preferably, the compounds of the invention are useful in the treatment of CNS cancer (including glioblastoma multiforme, glioma, neuroblastoma, medulloblastoma, DIPG and secondary brain tumours such as brain metastasis, , sarcoma (including osteosarcoma, rhabdomyosarcoma, Kaposi’s sarcoma, leiomyosarcoma), bladder cancer, endometrial cancer, lung cancer (including small cell lung cancer, non-small cell lung cancer), breast cancer, squamous cancer (including squamous cell carcinoma head and neck), colorectal cancer (including colon cancer, rectal cancer, anal cancer), gastric cancer, or ovarian cancer (including high grade serous ovarian cancer). The term “treatment” and “treating” as used herein may include prophylaxis of the named disorder or condition, or amelioration or elimination of the disorder or condition once it has been established. The term “prevention” refers to prophylaxis of the named disorder or condition. As used herein, the terms “administration” or “administering” mean a route of administration for a compound disclosed herein. Exemplary routes of administration include, but are not limited to, oral, intravenous, intraperitoneal, intraarterial, and intramuscular. The preferred route of administration can vary depending on various factors, e.g. the components of the pharmaceutical composition comprising a compound disclosed herein, site of the potential or actual disease and severity of disease. The terms “subject” and “patient” are used herein interchangeably. They refer to a human or another mammal (e.g., mouse, rat, rabbit, dog, cat, cattle, swine, sheep, horse or primate) that can be afflicted with or is susceptible to a disease or disorder but may or may not have the disease or disorder. It is preferred that the subject is human. “A therapeutically effective amount” refers to an amount of a compound of the invention that confers a therapeutic effect on the treated subject. The therapeutic effect may be objective (i.e. measurable by some test or marker) or subjective (i.e. subject gives an indication of or feels an effect). Methods delineated herein include those wherein the subject is identified as in need of a particular stated treatment. Identifying a subject in need of such treatment can be in the judgment of a subject or a health care professional and can be subjective (e.g. opinion) or objective (e.g. measurable by a test or diagnostic method). In other aspects, the methods herein include those further comprising monitoring subject response to the treatment administrations. Such monitoring may include periodic sampling of subject tissue, fluids, specimens, cells, proteins, chemical markers, genetic materials, etc. as markers or indicators of the treatment regimen. In other methods, the subject is pre-screened or identified as in need of such treatment by assessment for a relevant marker or indicator of suitability for such treatment. The compounds of the invention may be used as a mono therapy. They may also be used as part of a combination therapy. When used as a combination therapy they may be administered in combination with one or more of anticancer treatments including ionising radiation; a DNA topoisomerase I or II inhibitor; an antimetabolite or thymidylate synthase inhibitor; an agent related to the DNA damage and repair mechanism; a microtubule targeted agent; platinum based antineoplastic agents; alkylating agents and immune checkpoint inhibitors. Anticancer agents related to the DNA damage and repair mechanism include, but are not limited to, Wee1 inhibitors such as Adavosertib; PARP inhibitors such as Olaparib, Veliparib, Niraparib, Rucaparib, Talazoparib and senaparib; ATR inhibitors such as ceralasetib, gartisertib; HDAC inhibitors such as entinostat, vorinostat; PARG inhibitors such as PDD00017273 and JA2131; and ATM inhibitors such as AZD0156, AZD1390. Topoisomerase inhibitors are exemplified by doxorubicin, irinotecan, camptothesin and etoposide. Antimetabolites are exemplified by gemcitabine, pemetrexed and cytarabine. Platinum based antineoplastic agents are exemplified by cisplatin and carboplatin. Alkylating agents are exemplified by temozolomide. Immune checkpoint inhibitors are exemplified by ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab and cemiplimab. Other chemotherapy agents which may be used in combination therapy include paclitaxel, MEK inhibitors such as binimetinib, cobimetinib and trametinib, farnesyltransferase inhibitors such as tipifarnib and rapamycin. As used herein, being “administered in combination” with one or more anticancer treatments means that the compounds are administered concomitantly or sequentially and in any suitable order, as will be appreciated by the skilled person. The invention provides a method of monitoring treatment progress. The method includes the step of determining a level of diagnostic marker (Marker) (e.g. any target or cell type delineated herein modulated by a compound herein) or diagnostic measurement (e.g. screen, assay) in a subject suffering from or susceptible to a disorder or symptoms thereof delineated herein, in which the subject has been administered a therapeutic amount of a compound herein sufficient to treat the disease or symptoms thereof. The level of Marker determined in the method can be compared to known levels of Marker in either healthy normal controls or in other afflicted patients to establish the subject’s disease status. In preferred features of the invention, a second level of Marker in the subject is determined at a time point later than the determination of the first level, and the two levels are compared to monitor the course of disease or the efficacy of the therapy. In certain preferred features of the invention, a pre- treatment level of Marker in the subject is determined prior to beginning treatment according to this invention; this pre-treatment level of Marker can then be compared to the level of Marker in the subject after the treatment commences, to determine the efficacy of the treatment. A level of Marker or Marker activity in a subject may be determined at least once. Comparison of Marker levels, e.g., to another measurement of Marker level obtained previously or subsequently from the same patient, another patient, or a normal subject, may be useful in determining whether therapy according to the invention is having the desired effect, and thereby permitting adjustment of dosage levels as appropriate. Determination of Marker levels may be performed using any suitable sampling/expression assay method known in the art or described herein. Preferably, a tissue or fluid sample is first removed from a subject. Examples of suitable samples include blood, urine, tissue, mouth or cheek cells, and hair samples containing roots. Other suitable samples would be known to the person skilled in the art. Determination of protein levels and/or mRNA levels (e.g., Marker levels) in the sample can be performed using any suitable technique known in the art, including, but not limited to, enzyme immunoassay, is ELISA, radiolabelling/assay techniques, blotting/chemiluminescence methods, real-time PCR, and the like. Compounds of the invention may be disclosed by the name or chemical structure. If a discrepancy exists between the name of a compound and its associated chemical structure, then the chemical structure prevails. The invention will now be further illustrated by the following non-limiting examples. The specific examples below are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. Without further elaboration, it is believed that one skilled in the art can, based on the description herein, utilise the present invention to its fullest extent. All references and publications cited herein are hereby incorporated by reference in their entirety. PREPARATION OF COMPOUNDS OF THE INVENTION The compounds of the invention may be prepared by, or in analogy with, conventional methods. The preparation of intermediates and compounds according to the examples of the present invention may in particular be illuminated by the following Schemes. Definitions of variables in the structures in schemes herein are commensurate with those of corresponding positions in the formulae delineated herein. The following abbreviations have been used: AcOH acetic acid AdBrettPhos 2-(di-1-adamantylphosphino)-3,6-dimethoxy-2',4',6'-tri-i-pro pyl- 1,1'-biphenyl AdBrettPhos Pd G3 methanesulfonato[2-(di-1-adamantylphosphino)-3,6-dimethoxy- 2',4',6'-tri-i-propyl-1,1'-biphenyl](2'-amino-1,1'-biphenyl- 2- yl)palladium(II) aq aqueous BCRP breast cancer resistance protein BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene Boc tert-butyloxycarbonyl n-BuLi n-butyl lithium Cbz benzyloxycarbonyl CNS Central nervous system Cu(OAc)2 copper(II) acetate Cu(OTf)2 copper(II) trifluoromethanesulfonate DAD diode-array detector DAST (diethylamino)sulfur trifluoride DCM dichloromethane DEA N,N-diethylaniline DIAD diisopropyl azodicarboxylate DIEA N,N-diisopropylethylamine DMF N,N-dimethylformamide DMSO dimethyl sulfoxide DXN 1,4-dioxane EDTA ethylenediaminetetraacetic acid Ephos dicyclohexyl(3-isopropoxy-2′,4′,6′-triisopropyl-[1,1� �-biphenyl]-2- yl)phosphane Ephos Pd G4 methanesulfonato{dicyclohexyl[3-(1-methylethoxy)-2',4',6'-tr is(1- methylethyl)[1,1'-biphenyl]-2-yl]phosphine}(2'-methylamino-1 ,1'- biphenyl-2-yl)palladium(II) ES ⁺ electrospray ionisation EtI iodoethane Et3N triethylamine EtOAc ethyl acetate EtOH ethanol Ex. example FA formic acid h hour(s) HBD H-bond donor HEPES N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid Hex hexane HPLC high-performance liquid chromatography Int. intermediate IPA isopropyl alcohol IV intravenous KOAc potassium acetate LCMS liquid chromatography-mass spectrometry mCPBA 3-chloroperbenzoic acid MDCK Madin-Darby canine kidney MDR1 multidrug resistance protein 1 MeCN acetonitrile MeI iodomethane MeOH methanol Me4tBuXPhos 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′- triisopropyl- 1,1′-biphenyl Min minute(s) MTBE methyl tert-butyl ether NaOAc sodium acetate NaOtBu sodium tert-butoxide NP normal phase n/r not recorded OTf trifluoromethanesulfonate Papp apparent permeability coefficient PDA photodiode-array detector Pd2dba3 tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)Cl2 [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II ) Pd(dppf)Cl2·DCM [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II ), complex with dichloromethane PE petroleum ether P-gp P-glycoprotein PhMe toluene PPh3 triphenylphosphine Prep-HPLC preparative high-performance liquid chromatography Prep-SFC preparative supercritical fluid chromatography Prep-TLC preparative thin layer chromatography RP reverse phase RT room temperature Rt retention time sat saturated SFC supercritical fluid chromatography STAB sodium triacetoxyborohydride tBuXPhos Pd G3 [(2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1� �-biphenyl)-2-(2′- amino-1,1′-biphenyl)] palladium(II) methanesulfonate TFA trifluoroacetic acid THF tetrahydrofuran tPSA topological polar surface area UPLC ultra-performance liquid chromatography XPhos 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl XPhos Pd G3 (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′- biphenyl)[2-(2′- amino-1,1′-biphenyl)]palladium(II) methanesulfonate Scheme 1: General synthetic routes for the preparation of compounds of Formula (I) Q ¹ X Y X Y R1 N H ₂ N 1-1 ^Br N N ^Br H N N N HN N N N N N X N X X Y Y X Y 1 Y M O ^M 2 R ¹ R ¹ B ^O 1-3 (I) XY X Y R1 1-2 wherein R1 , X and Y are as defined herein, Q1 is halo, and M ¹ and M ² are H, alkyl or M1 and M2 together may form a ring, such as in pinacol esters. Compounds of Formula (I) can be prepared by Buchwald-Hartwig cross-coupling reactions of compounds of general formula 1-3 with 5-aminopyrazine-2- carbonitrile. Compounds of formula 1-3 can be prepared from compounds of general formula 1-1 by SNAr reaction with 4-bromo-1H-imidazole. Alternatively, compounds of general formula 1-3 can be prepared from compounds of general formula 1-2 by Chan-Lam reaction with 4-bromo-1H-imidazole. Compounds of general formula 1-2 can be prepared from commercially available boronic acid/ester reagents of the same general formula but with suitable functional handles at R1 , X or Y, using standard chemistry reactions including Mitsunobu, SNAr, and reductive amination reactions. Alternatively, compounds of general formula 1-2 can be prepared from compounds of general formula 1-1 (where Q1 is Br) by transformation of suitable functional handles at R1 , X or Y by standard chemistry reactions including lithium-halogen exchange followed by reaction with a suitable electrophile and alkylation reactions, then conversion of Br (Q1) to the corresponding boronic acid/ester. Compounds of general formulae 1-3 or (I) can be converted into another compound of the same formula using standard chemistry reactions in one or more synthetic steps. For example, if R1 , X or Y contains a suitable halogen, then SNAr or Buchwald-Hartwig coupling reactions with the appropriate commercially available amine, or amines of general formula 2-2 (Scheme 2), can be used to give other compounds of general formulae 1-3 or (I). Alternatively, if R1 , X or Y contains a suitable aldehyde or ketone then reductive amination or carbonyl reduction reactions can be performed to give other compounds of general formulae 1-3 or (I). Alternatively, if R1 , X or Y contains a suitable OH group then Mitsunobu, Appel, alkylation or oxidation reactions can be performed to give other compounds of general formulae 1-3 or (I). Alternatively, if R1 , X or Y contains a suitable amine then N-oxidation, reductive amination, or alkylation reactions can be employed to give other compounds of general formulae 1-3 or (I). Where appropriate, amines can be installed via the corresponding NO2 group using standard chemistry transformations, or via SN2 reaction with a suitable reactant. Standard protecting group strategies can be applied as needed at any stage to facilitate the chemical transformations mentioned above. Where compounds contain one or more chiral centres, compounds can be made as racemates, as single enantiomers, or as diastereomeric mixtures of known or unknown absolute stereochemistry. Mixtures of enantiomers or diastereomers may be optionally separated by standard techniques at any stage in the synthetic sequence. Scheme 2: General synthetic routes for preparation of amines of general formula 2-2 2-1 2-2 wherein PG is a protecting group, and Q2 is H or methyl. Compounds of general formula 2-2 can be prepared from compounds of general formula 2-1 by reductive amination or alkylation followed by protecting group (PG) removal using standard conditions. Amines of general formula 2-2 can be reacted with intermediates of general formula 1-3 (Scheme 1, where R1 is a halogen) by standard Buchwald-Hartwig coupling reactions to give other compounds of general formula 1-3. EXAMPLES AND INTERMEDIATE COMPOUNDS Experimental methods All reactants and reagents were sourced commercially unless otherwise stated, in which case synthetic routes have been provided. All reagents were commercial- grade and were used as received without further purification unless otherwise specified. Reagent-grade solvents were used unless otherwise specified. Anhydrous solvents were used where appropriate. Solvent ratios are by volume. Reactions were conducted at RT unless otherwise specified. n-BuLi was used as a 2.5M solution in hexanes unless otherwise stated. Formaldehyde was used as a 37% by weight solution in water unless otherwise stated. NaH was used as a 60% dispersion in mineral oil unless otherwise stated. The reactions facilitated by microwave heating were performed on a Biotage Initiator+ system using process vials fitted with aluminium caps and septa. Amounts of reagents used and product yields were typically adjusted for purity where known. The Intermediates and Examples were named using IUPAC nomenclature. Column chromatography was performed using Teledyne ISCO CombiFlash RF200, CombiFlash RF+ or Combiflash RF+ Lumen systems equipped with RediSep® Rf, RediSep® Rf C18 Reverse Phase, or RediSep® Silver silica columns. Preparative RP HPLC was performed on either a Teledyne Isco ACCQPrep HP125 system with 200-400nm UV variable wavelength detector and a CombiFlash® PurIon™ S mass spectrometer, or an ACCQPrep HP150 system with 200-400nm UV variable wavelength detector, equipped with Avantor® ACE® 5 AQ, 100 x 21.2mm, 5µm columns, Avantor® ACE® SuperC18™, 100 x 21.2mm, 5µm columns, or Phenomenex® Kinetex® EVO C18, 100 x 21.2mm, 5µm columns. For RP column chromatography and RP HPLC modifiers used included TFA, FA and NH ₃ . Catch and elute purification was performed using Biotage ISOLUTE® Flash SCX-2 cartridges unless otherwise stated. A typical catch-and- elute procedure was to dissolve the crude material in DCM, load the solution onto the cartridge, wash with MeOH, elute with approximately 1N NH3 in MeOH then concentrate in vacuo. Chiral prep-HPLC was performed using a Gilson GX-281 chiral prep-HPLC with a 159 UV-VIS detector and 322 pump using the following methods: Chiral Prep-HPLC Method 1: Column: CHIRALPAK IG, 2×25 cm, 5μm; Mobile Phase A: Hex: MTBE = 1: 1 (0.5% 2M NH-MeOH), Mobile Phase B: MeOH Chiral Prep-HPLC Method 2: Column: CHIRALCEL AY-H, 2×25cm, 5μm; Mobile Phase A: Hex (10mM NH-MeOH), Mobile Phase B: EtOH Chiral Prep-HPLC Method 3: Column: CHIRAL ART Cellulose-SZ, 3×25cm, 5μm; Mobile Phase A: Hex (10mM NH-MeOH), Mobile Phase B: EtOH Chiral Prep-HPLC Method 4: Column: CHIRALPAK 1A-3, 4.6×5mm, 3μm; Mobile Phase A: MTBE (0.1% DEA): EtOH=70:30 Chiral Prep-HPLC Method 5: Column: CHIRALPAK ID-3, 4.6×50mm 3μm; Mobile Phase A: MTBE (0.1% DEA): MeOH=70:30 Chiral Prep-HPLC Method 6: Column: CHIRALPAK IA, 2.12×15cm, 5μm; Mobile Phase A: MTBE (10mM NH-MeOH), Mobile Phase B: MeOH Chiral Prep-HPLC Method 7: Column: CHIRAL ART Amylose-SA, 3×25cm, 5μm; Mobile Phase A: MTBE: DCM=1: 1 (10mM NH), Mobile Phase B: MeOH Chiral Prep-HPLC Method 8: Column: CHIRAL ART Amylose-SA, 3×25cm, 5μm; Mobile Phase A: MTBE (10mM NH-MeOH), Mobile Phase B: MeOH Chiral Prep-HPLC Method 9: Column: CHIRALPAK ID, 3×25cm, 5μm; Mobile Phase A: MTBE (2mM NH-MeOH), Mobile Phase B: MeOH Chiral Prep-HPLC Method 10: Column: CHIRALPAK IA-3, 4.6×50mm, 3μm; Mobile Phase A: MTBE(0.1% DEA): MeOH = 50: 50 Prep-SFC was performed on a Waters SFC-150 with a Waters 2489 UV detector, a Waters preparative fraction selector, a Waters 2545 co-solvent pump and a Waters P200X CO2 pump using the following methods: Prep-SFC Method 1: Column: CHIRALPAK IH, 3×25cm, 5µm; Mobile Phase A: CO, Mobile Phase B: MeOH Prep-SFC Method 2: Column: CHIRALPAK IH, 3×25cm, 5µm; Mobile Phase A: CO, Mobile Phase B: MeOH (0.1% 2M NH-MeOH) Prep-SFC Method 3: Column: (R,R)-WHELK-01-Kromasil, 5×25cm, 5μm; Mobile Phase A: MTBE: DCM=1: 1, Mobile Phase B: MeOH Prep-SFC Method 4: Column: Lux 5μm Cellulose-3, 2.12×25cm, 5μm; Mobile Phase A: Hex (10mM NH-MeOH), Mobile Phase B: EtOH Prep-SFC Method 5: Column: CHIRALPAK IA, 2×25cm, 5μm; Mobile Phase A: MeOH: DCM=2: 1 (0.1% 2M NH-MeOH), Mobile Phase B: MeOH Prep-SFC Method 6: Column: CHIRALPAK ID, 2×25cm, 5μm; Mobile Phase A: MTBE (10mM NH-MeOH), Mobile Phase B: MeOH Compound analysis was performed by UPLC, HPLC and LCMS. UPLC data was collected using an Agilent 1290 Infinity or Infinity II system with DAD using a Phenomenex Kinetex XB-C18 column. HPLC and LCMS data was collected using a Waters ACQUITY H-class HPLC with Phenomenex Kinetex XB-C18 column and ACQUITY QDa mass detector connector, or a Shimadzu LCMS-2020 system with PDA: SPD-M20A or SPD-MP40. INTERMEDIATES Intermediate 1 2- To 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.00g, 4.50mmol), tert- butyl N-(3-hydroxypropyl)carbamate (1.19g, 6.8mmol) and PPh3 (1.79g, 6.82mmol) in THF (20mL) at 0°C was added DIAD (1.38g, 6.82mmol) dropwise. The mixture was allowed to warm to RT and stir for 4h. The mixture was quenched with water then concentrated in vacuo and purified via RP column chromatography to afford the title compound (570mg, 33.3%) as a light-yellow solid. LCMS (ES+): 378.3 [MH]+. Intermediate 2 (4-(Morpholinomethyl)phenyl)boronic acid 4-Formylphenylboronic acid (1.00g, 6.67mmol) and morpholine (0.58g, 6.67mmol) in MeOH (15mL) was allowed to stir at RT for 1h. To the mixture was added NaBH ₃ CN (0.42g, 6.67mmol) at 0°C. The mixture was then allowed to warm to RT and stir for a further 12h. The reaction was quenched with water, extracting with EtOAc (3×100mL). The combined organic layers were washed with brine (100mL), dried (Na2SO4), and concentrated in vacuo. Purification via RP column chromatography afforded the title compound (451mg, 30.6%) as a white solid. LCMS (ES+): 225.3 [MH]+. Intermediate 3 (4-(4-Fluoro-1-methylpiperidin-4-yl)phenyl)boronic acid Step 1: To dibromobenzene (2.00g, 8.48mmol) in THF (20mL) was added n-BuLi (3.40mL, 8.50mmol) dropwise at -78°C. The mixture was then stirred for 30min before addition of 1-methylpiperidin-4-one (0.96g, 8.48mmol) dropwise. The mixture was allowed to warm to RT and stir for a further 1h. Reaction quenched with water, extracting with EtOAc (2×20mL). The combined organic layers were washed with brine (2×10mL), dried (Na2SO4), and concentrated in vacuo. Purification via RP column chromatography afforded 4-(4-bromophenyl)-1- methylpiperidin-4-ol (1.66g, 72.5%) as a yellow oil. LCMS (ES+): 270.3 [MH]+. Step 2: To a mixture of 4-(4-bromophenyl)-1-methylpiperidin-4-ol (1.00g, 3.70mmol) in THF (10mL) was added DAST (1.19g, 7.40mmol) dropwise at -78°C under N ₂ . The mixture was allowed to warm to RT and stirred for 5h. Reaction quenched with ice water, extracting with EtOAc (2×10mL). The combined organic layers were washed with water (2×10mL), dried (Na2SO4), and concentrated in vacuo. Purification via NP column chromatography afforded 4-(4-bromophenyl)-4- fluoro-1-methylpiperidine (760mg, 75.4%) as a brown solid. LCMS (ES+): 272.3 [MH]+. Step 3: A mixture of 4-(4-bromophenyl)-4-fluoro-1-methylpiperidine (760mg, 2.79mmol), bis(pinacolato)diboron (1.42g, 5.58mmol), Pd(dppf)Cl2·DCM (1.14g, 1.40mmol), KOAc (548mg, 5.58mmol) in DXN (10mL) was stirred for 16h at 100°C under N ₂ . The mixture was filtered, washing with DXN, the filtrate was then concentrated in vacuo. Purification via RP column chromatography afforded 4- fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan -2- yl)phenyl)piperidine (400mg, 44.9%) as a yellow oil. LCMS (ES+): 320.2 [MH]+. Step 4: A mixture of 4-fluoro-1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl)piperidine (400mg, 1.26mmol) and NaIO ₄ (810mg, 3.76mmol) in THF (4.0mL) and water (1.0mL) was stirred for 4h. The mixture was filtered, washing with MeOH, the filtrate was then concentrated in vacuo. Purification via RP column chromatography afforded the title compound (240mg, 80.8%) as a yellow oil. LCMS (ES+): 238.1 [MH]+. Intermediate 4 (4-(4-Methylmorpholin-2-yl)phenyl)boronic acid Step 1: To a mixture of methylethanolamine (1.62g, 21.6mmol) was added FA (1.0mL) dropwise at 0°C under N ₂ . Then 2-bromo-1-(4-bromophenyl) ethanone (3.00g, 10.8mmol) was added and the mixture was heated to 100°C and allowed to stir for 16h. The reaction was quenched with water, extracting with EtOAc (50mL). Excess K2CO3 was added to the aqueous which was further extracted with EtOAc (3×100mL). The combined organic layers were washed with brine (50mL), dried (Na2SO4), and concentrated in vacuo. Purification via RP column chromatography afforded 2-(4-bromophenyl)-4-methylmorpholine (1.42g, 51.4%) as a yellow oil. LCMS (ES+): 256.1 [MH]+. Step 2: 2-(4-Bromophenyl)-4-methylmorpholine (1.42g, 5.54mmol), bis(pinacolato)diboron (2.11g, 8.32mmol,), Pd(dppf)Cl2·DCM (230mg, 0.282mmol) and NaOAc (1.53mg, 18.7mmol) in DXN (20mL) was stirred for 16h at 80°C under N ₂ . The mixture was concentrated in vacuo and purified via RP column chromatography to afford 4-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl)morpholine (704mg, 41.9%) as a brown oil. LCMS (ES+): 304.3 [MH]+. Step 3: 4-Methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl)morpholine (704mg, 2.32mmol) and NaIO4 (2.44g, 11.4mmol) in THF (20mL) and water (4.0mL) was stirred for 36h. The mixture was concentrated in vacuo and purified via RP column chromatography to afford the title compound (432mg, 84.1%) as a yellow solid. LCMS (ES+): 222.2 [MH]+. Intermediate 5 (4-(1-(tert-Butoxycarbonyl)azetidin-3-yl)phenyl)boronic acid To tert-butyl 3-(4-bromophenyl)azetidine-1-carboxylate (500mg, 1.60mmol) in THF (10mL) was added n-BuLi (0.75mL, 1.92mmol) dropwise at -78°C under N ₂ . The mixture was allowed to stir for 30min before addition of triisopropyl borate (451mg, 2.40mmol) dropwise. The mixture was then allowed to warm to RT and stir for a further 2h. The mixture was concentrated in vacuo and purified via NP column chromatography to afford the title compound (227mg, 51.2%) as a yellow oil. LCMS (ES+): 278.1 [MH]+. Intermediate 6 (6-(4-Methyl-1,4-diazepan-1-yl)pyridin-3-yl)boronic acid 6-Fluoropyridin-3-ylboronic acid (3.00g, 21.3mmol), N-methylhomopiperazine (4.86mL, 42.6mmol) and K2CO3 (4.41g, 31.9mmol) in DMF (50mL) was heated to 110°C and allowed to stir for 16h. The mixture was concentrated in vacuo to afford the title compound (2.80g, 56.0%) as a yellow solid. LCMS (ES+): 236.1 [MH]+. Intermediate 7 (3-Fluoro-4-(4-methylpiperazin-1-yl)phenyl)boronic acid Step 1: 1-(4-Bromo-2-fluorophenyl)-4-methylpiperazine (1.00g, 3.66mmol), bis(pinacolato)diboron (1.39g, 5.48mmol), Pd(dppf)Cl2 (26.8mg, 0.37mmol) and NaOAc (601mg, 7.32mmol) in DXN (25mL) was heated to 100°C and allowed to stir for 12h under N ₂ . The mixture was concentrated in vacuo to afford crude 1-(2- fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl )-4-methylpiperazine which was used in the next step without further purification. LCMS (ES+): 321.2 [MH]+. Step 2: Crude 1-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p henyl)- 4-methylpiperazine, and NaIO ₄ (3.22g, 15.1mmol) in THF (20mL) was heated to 40°C and allowed to stir for 5h. The mixture was filtered, washing with EtOAc, the filtrate was then concentrated in vacuo. Purification via RP column chromatography afforded the title compound (130mg, 19% yield over 2 steps) as a light-yellow oil. LCMS (ES+): 239.2 [MH]+. Intermediate 8 (2-(3-((tert-Butoxycarbonyl)amino)propoxy)-6-methoxyphenyl)b oronic acid Step 1: 2-Bromo-3-methoxyphenol (3.00g, 14.8mmol), tert-butyl N-(3- bromopropyl)carbamate (3.52g, 14.8mmol), NaI (2.21g, 14.8mmol) and K ₂ CO ₃ (4.08g, 29.6mmol) in DMF (20mL) was stirred for 16h at 60°C. Reaction quenched with water extracting with EtOAc (2×200mL). The combined organics were washed with brine, dried (Na2SO4), and concentrated in vacuo. Purification via NP column chromatography afforded tert-butyl (3-(2-bromo-3- methoxyphenoxy)propyl)carbamate (3.20g, 60.1%) as a colourless oil. LCMS (ES+): 360.1 [MH]+. Step 2: To tert-butyl (3-(2-bromo-3-methoxyphenoxy)propyl)carbamate (1.00g, 2.78mmol) in THF (10mL) was added n-BuLi (2.50mL, 6.25mmol) dropwise at - 78°C under N ₂ . To the mixture was added trimethyl borate (288mg, 2.78mmol) dropwise. The mixture was then allowed to warm to RT and stir for a further 1h. Reaction quenched with water, extracting with EtOAc (2×100mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated in vacuo. Purification via NP column chromatography afforded the title compound (460mg, 51.0%) as a colourless oil. LCMS (ES+): 326.2 [MH]+. Intermediate 9 (3R,5R)-N,N,5-Trimethylpyrrolidin-3-amine Step 1: tert-Butyl (2R,4R)-4-amino-2-methylpyrrolidine-1-carboxylate (1.00g, 4.99mmol) and formaldehyde (1.12mL, 15.0mmol) in MeOH (20mL) was stirred at RT for 30min. The mixture was cooled to 0°C and STAB (4.23g, 20.0mmol) was added in portions. The mixture was then allowed to warm to RT and stir for a further 2h. The mixture was concentrated in vacuo and purified via NP column chromatography. Drying in a vacuum oven at 60°C for 1h afforded tert-butyl (2R,4R)-4-(dimethylamino)-2-methylpyrrolidine-1-carboxylate (778mg, 68.2%) as a colourless oil. LCMS (ES+): 229.2 [MH]+. UPLC: Rt 3.23min, 100% purity. Step 2: To tert-butyl (2R,4R)-4-(dimethylamino)-2-methylpyrrolidine-1-carboxylate (778mg, 3.40mmol) in DCM (11mL) was added TFA (2.5mL). The mixture was allowed to stir for 2h. The mixture was concentrated in vacuo giving crude title compound (763mg) as a brown oil which was used directly in the next step without further purification. LCMS (ES+): 129.1 [MH]+. Intermediate 10 (2R,4R)-4-(Azetidin-1-yl)-2-methylpyrrolidine Step 1: tert-Butyl (2R,4R)-4-amino-2-methylpyrrolidine-1-carboxylate (3.00g, 15.0mmol), 1,3-dibromopropane (2.50mL, 24.6mmol), and K ₂ CO ₃ (10.4g, 75.2mmol) in MeCN (200mL) was heated to 90°C and stirred for 21h. The mixture was filtered, washing with MeCN, the filtrate was concentrated in vacuo and purified via NP column chromatography to afford crude tert-butyl (2R,4R)-4- (azetidin-1-yl)-2-methylpyrrolidine-1-carboxylate which was used directly in the next step without further purification. Step 2: To crude tert-butyl (2R,4R)-4-(azetidin-1-yl)-2-methylpyrrolidine-1- carboxylate in DCM (12mL) was added TFA (4.0mL). The mixture was concentrated in vacuo and the crude material was purified via a catch and release cartridge to afford the title compound (617mg, 29.4% over 2 steps) as a brown oil. LCMS (ES+): 141.0 [MH]+. Intermediate 11 (R)-3-(Azetidin-1-yl)pyrrolidine Step 1: To benzyl (R)-3-aminopyrrolidine-1-carboxylate (15.0g, 68.1mmol) and DIEA (35.6mL, 205mmol) in MeCN (500mL) was added 1,3-dibromopropane (11.0mL, 108mmol) dropwise. The mixture was then heated to 80°C and allowed to stir for 12h. The mixture was concentrated in vacuo and purified via RP column chromatography to afford benzyl (R)-3-(azetidin-1-yl)pyrrolidine-1-carboxylate (6.70g, 37.8%) as a yellow oil. LCMS (ES+): 261.2 [MH]+. Step 2: To benzyl (R)-3-(azetidin-1-yl)pyrrolidine-1-carboxylate (6.30g, 24.2mmol) in EtOAc (200mL) was added Pd/C (10% by weight, 6.31g, 5.93mmol). The mixture was allowed to stir for 3h under an atmosphere of H ₂ . The mixture was filtered washing with EtOAc, the filtrate was concentrated in vacuo to afford crude title compound (2.60g) as a yellow oil which was used in the next step without further purification. LCMS (ES+): 127.3 [MH]+. Intermediate 12 1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-4-methylpiperazine A mixture of 4-(4-methylpiperazin-1-yl)phenylboronic acid (749mg, 3.40mmol), 4- bromo-1H-imidazole (200mg, 1.36mmol), NaOH (82.0mg, 2.04mmol) and CuCl2 (22.0mg, 0.16mmol) in MeOH (10mL) was stirred overnight at 60°C under O2. The mixture was cooled to RT, filtered, and the filter cake washed with MeOH (2×10mL). The filtrate was concentrated in vacuo and purified via prep-TLC (DCM/MeOH 10:1) to afford the title compound (220mg, 50.3%) as a yellow solid. LCMS (ES+): 321.10 [MH]+. Intermediate 13 tert-Butyl (3-(2-(4-bromo-1H-imidazol-1-yl)phenoxy)propyl)carbamate Intermediate 13 was prepared similarly to Intermediate 12 via Chan-Lam coupling of Intermediate 1 with 4-bromo-1H-imidazole using CuCl2 and NaOH then purification via NP column chromatography to afford the title compound (40.1mg, 38.2%) as a white solid. LCMS (ES+): 395.9 [MH]+. Intermediate 14 (4-(4-Bromo-1H-imidazol-1-yl)phenyl)(4-methylpiperazin-1-yl) methanone A mixture of 4-(4-methylpiperazine-1-carbonyl)phenylboronic acid (500mg, 1.51mmol), 4-bromo-1H-imidazole (300mg, 2.04mmol), boric acid (190mg, 3.07mmol), and Cu(OAc) ₂ (85.0mg, 0.47mmol) in MeCN (2.5mL) was heated in a sealed tube at 80°C for 28h. The reaction mixture was diluted with EtOAc (20mL) and filtered through Celite®, washing with further EtOAc. The filtrate was then concentrated in vacuo and purified via NP column chromatography to afford the title compound (121mg, 21.9%) as a colourless gum. LCMS (ES+): 349.1 [MH]+. Intermediate 15 4-(4-(4-Bromo-1H-imidazol-1-yl)benzyl)morpholine B ^r To a stirred solution of Intermediate 2 (412mg, 1.86mmol) and 4-bromo-1H- imidazole (274mg, 1.86mmol) in DMF (15mL) were added DIEA (723mg, 5.59mmol) and Cu(OAc) ₂ (677mg, 3.73mmol) at RT. The resulting mixture was stirred for 12h at 60°C under O2 then cooled to RT, filtered, and the filtrate concentrated in vacuo and purified via NP column chromatography to afford the title compound (155mg, 25.8%) as a red solid. LCMS (ES+): 322.15 [MH]+. Intermediates 16 to 20 Intermediates 16 to 20 were prepared similarly to Intermediate 15 via Chan-Lam coupling of 4-bromo-1H-imidazole with the appropriate boronic acid or boronic ester using Cu(OAc)2 and either DIEA or pyridine as the base; see Table 1 below. Table 1: Chan-Lam Coupling of 4-bromo-1H-imidazole with the appropriate boronic acid or boronic ester using Cu(OAc)2 S ; ; 1 %; 3 %; 3 ; ; 1 ; %; 1 Intermediate 21 4-Bromo-1-(4-bromo-2-methoxyphenyl)-1H-imidazole (4-Bromo-2-methoxy-phenyl)boronic acid (4.92g, 21.3mmol), 4-bromo-1H- imidazole (4.70g, 32.0mmol), pyridine (5.15mL, 63.9mmol) and Cu(OTf)2 (15.4g, 42.6mmol) in DMF (30mL) were heated to 40°C and stirred for 17h. The reaction mixture was concentrated in vacuo, diluted with EtOAc (30mL) and water (30mL), the phases separated, and the aqueous phase further extracted with EtOAc (30mL). The combined organic phases were washed with brine (30mL), concentrated in vacuo and purified via NP column chromatography to afford the title compound (1.36g, 19.2%) as a white solid. LCMS (ES+): 330.7 [MH]+. Intermediates 22 to 38 Intermediates 22 to 38 were prepared similarly to Intermediate 21 via Chan-Lam coupling of 4-bromo-1H-imidazole with the appropriate boronic acid or boronic ester using Cu(OTf)2 and either pyridine, DIEA or Et3N as the base; see Table 2 below. Table 2: Chan-Lam Coupling of 4-bromo-1H-imidazole with the appropriate boronic acid or boronic ester using Cu(OTf) ₂ S %; 1 %; 2 2; %; 1 ; %; 5 %; 3 ; ; 9 4; %; 2 %; 1 ; %; 5 ; ; 2 2; %; 0 ; ; 6 7; %; 2 ; %; 7; %; 9 ; ; 1 ; ; 0 Intermediate 39 tert-Butyl 6-(4-(4-bromo-1H-imidazol-1-yl)-3-methoxyphenoxy)-2- azaspiro[3.3]heptane-2-carboxylate To a stirred mixture of Intermediate 35 (650mg, 2.42mmol) in DMF (3.0mL) was added NaH (116mg, 4.83mmol) at 0°C. The resulting mixture was stirred at 0°C for 0.5h then tert-butyl 6-(methanesulfonyloxy)-2-azaspiro[3.3]heptane-2- carboxylate (1.05g, 3.62mmol) was added dropwise at 0°C. The resulting mixture was stirred for additional 2h at 80°C then concentrated in vacuo and purified via prep-TLC (PE/EtOAc 1:1) to afford the title compound (756mg, 67.4%) as a yellow oil. LCMS (ES+): 466.10 [MH]+. Intermediate 40 4-(4-Bromo-1H-imidazol-1-yl)-2-chlorobenzaldehyde A mixture of 4-bromo-1H-imidazole (200mg, 1.36mmol), 2-chloro-4- fluorobenzaldehyde (216mg, 1.36mmol) and K2CO3 (282mg, 2.04mmol) in DMSO (2.0mL) was stirred at 60°C for 16h. The reaction mixture was allowed to cool to RT, and poured into rapidly stirring water (15mL). The resulting solid was collected via filtration, washed with water (4×30mL), then dried in the vacuum oven at 50°C for 3h to afford the title compound (350mg, 77.3%) as a white solid. LCMS (ES+): 284.9 [MH]+. Intermediates 41 to 44 Intermediates 41 to 44 were prepared similarly to Intermediate 40 via nucleophilic aromatic substitution of the appropriate halogenated aromatic substrate with 4- bromo-1H-imidazole in DMSO using K2CO3 as the base; see Table 3 below. Table 3: Nucleophilic aromatic substitution of the appropriate halogenated aromatic substrate with 4-bromo-1H-imidazole S ; %; 9 %; 1 ; %; 6 ; %; 6 Intermediate 45 4-Bromo-1-(4-bromophenyl)-1H-imidazole A mixture of 4-bromo-1H-imidazole (5.00g, 34.0mmol), 1-bromo-4-fluorobenzene (7.50mL, 69.3mmol) and K ₃ PO ₄ (36.3g, 171mmol) in DMF (100mL) was heated to 150°C for 20h. The reaction mixture was slowly poured into rapidly stirring water (400mL), filtered, then the residue was washed with water (20mL) and dried in a vacuum oven at 60°C for 5h to afford the title compound (7.93g, 74.3%) as a white solid. LCMS (ES+): 300.8 [MH]+. Intermediates 46 to 48 Intermediates 46 to 48 were prepared similarly to Intermediate 45 via nucleophilic aromatic substitution of the appropriate halogenated aromatic substrate with 4- bromo-1H-imidazole in DMF using K3PO4 as the base; see Table 4 below. Table 4: Nucleophilic aromatic substitution of the appropriate halogenated aromatic substrate with 4-bromo-1H-imidazole S ; %; 7 %; 9 4; %; 9 Intermediate 49 5-Bromo-2-(4-bromo-1H-imidazol-1-yl)pyridine To a stirred mixture of 5-bromo-2-fluoropyridine (1.00g, 5.68mmol) and 4-bromo- 1H-imidazole (1.25g, 8.52mmol) in DMF (20mL) was added Cs ₂ CO ₃ (3.70g, 11.4mmol) at RT. The resulting mixture was stirred for 1h at 100°C then quenched with water (100mL), extracted with EtOAc (5×100mL) and the combined organic layers were washed with brine (50mL), dried (Na2SO4), concentrated in vacuo and purified via NP column chromatography to afford the title compound (1.10g, 63.9%) as a yellow solid. LCMS (ES+): 304.1 [MH]+. Intermediate 50 2-(4-Bromo-1H-imidazol-1-yl)-5-chloropyrazine To a solution of 4-bromo-1H-imidazole (493mg, 3.36mmol) in DMF (10mL) was added NaH (162mg, 4.05mmol) at 0°C. The mixture was stirred for 1h then 2,5- dichloro-pyrazine (500mg, 3.36mmol) was added. The mixture was warmed to 100°C, stirred for 1h then quenched via water and extracted with DCM (3×25mL). The combined organic layers were washed with brine, dried (Na ₂ SO ₄ ), concentrated in vacuo and purified via NP column chromatography to afford the title compound (400mg, 45.9%) as a light-yellow solid. LCMS (ES+): 259.0 [MH]+. Intermediate 51 4-(4-Bromo-1H-imidazol-1-yl)-3-methyl-5-(trifluoromethyl)ben zaldehyde To a stirred mixture of 4-fluoro-3-methyl-5-(trifluoromethyl)benzaldehyde (2.00g, 9.70mmol) and 4-bromo-1H-imidazole (2.14g, 14.6mmol) in MeCN (5.0mL) was added DIEA (3.38mL, 19.4mmol) dropwise at RT. The mixture was stirred at 80°C for 16h then concentrated in vacuo and purified via NP column chromatography to afford the title compound (1.30g, 40.2%) as a white solid. LCMS (ES+): 333.0 [MH]+. Intermediate 52 4-(4-Bromo-1H-imidazol-1-yl)-3,5-dimethylbenzaldehyde To a stirred mixture of 4-fluoro-3,5-dimethylbenzaldehyde (1.00g, 6.57mmol) and 4-bromo-1H-imidazole (1.93g, 13.1mmol) in DMF (50mL) was added K2CO3 (1.82g, 13.1mmol) at RT under N2. The resulting mixture was stirred for 2h at 100°C, quenched with water, extracted with EtOAc (3×25mL) then the combined organic layers were washed with brine, dried (Na2SO4), concentrated in vacuo and purified via NP column chromatography to afford the title compound (103mg, 5.60%) as a light-yellow powder. LCMS (ES+): 279.10 [MH]+. Intermediate 53 3-Bromo-6-(4-bromo-1H-imidazol-1-yl)-2-methylpyridine A solution of 3-bromo-6-fluoro-2-methylpyridine (2.00g, 10.5mmol), 4-bromo-1H- imidazole (2.19g, 14.9mmol) and DIEA (2.58g, 20.0mmol) in DMF (10mL) was stirred overnight at 100°C then quenched with water and extracted with EtOAc (3×10mL). The combined organic layers were washed with brine (3×10mL), dried (Na2SO4), concentrated in vacuo and purified via NP column chromatography to afford the title compound (356mg, 10.7%) as a white solid. LCMS (ES+): 317.9 [MH]+. Intermediate 54 5-Bromo-2-(4-bromo-1H-imidazol-1-yl)pyrimidine Intermediate 54 was prepared similarly to Intermediate 53 via nucleophilic aromatic substitution of 5-bromo-2-chloropyrimidine with 4-bromo-1H-imidazole in DMF using DIEA as the base then purification via NP column chromatography to afford the title compound (420mg, 17.8%) as a white solid. LCMS (ES+): 304.9 [MH]+. Intermediate 55 4-Bromo-1-(4-bromo-2-nitrophenyl)-1H-imidazole Intermediate 55 was prepared similarly to Intermediate 53 via nucleophilic aromatic substitution of 4-bromo-1-fluoro-2-nitrobenzene with 4-bromo-1H- imidazole in MeCN using DIEA as the base then purification via NP column chromatography to afford the title compound (6.30g, 93.2%) as a yellow solid. LCMS (ES+): 347.6 [MH]+. Intermediate 56 tert-Butyl (3S,4S)-3-((4-(4-bromo-1H-imidazol-1-yl)benzyl)oxy)-4- fluoropyrrolidine-1-carboxylate Step 1: To a solution of Intermediate 42 (1.00g, 3.98mmol) in MeOH (20mL) was added NaBH4 (301mg, 7.96mmol) at 0°C. The reaction mixture was stirred for 1h at RT then quenched with water (50mL) at 0°C and the resulting mixture was extracted with EtOAc (3×100mL). The combined organic layers were washed with brine (1×50mL), dried (Na ₂ SO ₄ ), and concentrated in vacuo to afford [4-(4- bromoimidazol-1-yl)phenyl]methanol (990mg, 98.2%) as a white solid. LCMS (ES+): 253.0 [MH]+. Step 2: To a stirred mixture of [4-(4-bromoimidazol-1-yl)phenyl]methanol (3.60g, 14.2mmol) and CBr ₄ (9.43g, 28.5mmol) in DCM (30mL) was added PPh ₃ (7.46g, 28.4mmol) at 0°C under N ₂ . The mixture was stirred for 4h at 0°C then concentrated in vacuo and purified via NP column chromatography to afford 4- bromo-1-[4-(bromomethyl)phenyl]imidazole (3.00g, 66.8%) as a white solid. LCMS (ES+): 316.8 [MH]+. Step 3: To a solution of tert-butyl (3S,4S)-3-fluoro-4-hydroxypyrrolidine-1- carboxylate (500mg, 2.44mmol) in DMF (10mL) was added NaH (128mg, 3.20mmol) at 0°C. The mixture was stirred for 15min then 4-bromo-1-[4- (bromomethyl)phenyl]imidazole (500mg, 1.58mmol) was added, the mixture warmed to RT, then stirred for 1h. The reaction was quenched with water (10mL), extracted with EtOAc (3×50mL) and the combined organic layers were washed with brine (3×10mL), dried (Na2SO4), concentrated in vacuo and purified via NP column chromatography to afford the title compound (530mg, 76.1%) as a yellow oil. LCMS (ES+): 439.9 [MH]+. Intermediate 57 tert-Butyl (3S,4R)-3-((4-(4-bromo-1H-imidazol-1-yl)benzyl)oxy)-4- fluoropyrrolidine-1-carboxylate Intermediate 57 was prepared similarly to Intermediate 56, via aldehyde reduction of Intermediate 42 using NaBH ₄ followed by Appel reaction using CBr ₄ and PPh ₃ , then alkylation with tert-butyl (3R,4S)-3-fluoro-4-hydroxypyrrolidine-1-carboxylate to afford the title compound (660mg, 94.7%) as a yellow solid. LCMS (ES+): 439.9 [MH]+. Intermediate 58 1-(4-(4-Bromo-1H-imidazol-1-yl)benzyl)-4-methylpiperazine To a stirred mixture of Intermediate 42 (600mg, 2.39mmol) and STAB (1.00g, 4.78mmol) in DCM (12mL) was added 1-methyl-piperazine (359mg, 3.58mmol) at RT under N2. The mixture was stirred for 2h then concentrated in vacuo and purified via NP column chromatography to afford the title compound (329mg, 41.1%) as a yellow solid. LCMS (ES+): 335.3 [MH]+. Intermediate 59 (R)-4-Bromo-1-(3-chloro-4-((3-fluoropyrrolidin-1-yl)methyl)p henyl)-1H- imidazole Intermediate 40 (50.0mg, 0.15mmol, 85.8% purity), (R)-(-)-3-fluoropyrrolidine·HCl (18.9mg, 0.15mmol) and MP-trimethylammonium cyanoborohydride resin (3.82mmol/g, 101mg, 0.38mmol) in IPA (1.5mL) and AcOH (150µL) was heated using a microwave reactor (100°C) for 25min. The reaction mixture was diluted with DCM (5.0mL), passed through a thin Celite® pad, concentrated in vacuo and purified via RP HPLC. The combined fractions were passed through a catch and elute cartridge to afford the title compound (26.0mg, 48.3%) as a colourless gum. LCMS (ES+): 357.6 [MH]+. Intermediate 60 (R)-4-Bromo-1-(2-fluoro-4-((3-fluoropyrrolidin-1-yl)methyl)- 6- methoxyphenyl)-1H-imidazole Intermediate 60 was prepared similarly to Intermediate 59 via reductive amination of Intermediate 43 with (R)-(-)-3-fluoropyrrolidine.HCl using MP- trimethylammonium cyanoborohydride resin to afford the title compound (26.0mg, 35.3%) as a colourless gum. LCMS (ES+): 371.7 [MH]+. Intermediate 61 (R)-4-Bromo-1-(2-fluoro-4-((3-fluoropyrrolidin-1-yl)methyl)p henyl)-1H- imidazole Intermediate 61 was prepared similarly to Intermediate 59 via reductive amination of Intermediate 44 with (R)-(-)-3-fluoropyrrolidine·HCl using MP- trimethylammonium cyanoborohydride resin to afford the title compound (34.0mg, 45.5%) as a colourless gum. LCMS (ES+): 341.6 [MH]+. Intermediate 62 (R)-4-Bromo-1-(4-((3-fluoropyrrolidin-1-yl)methyl)-2-methyl- 6- (trifluoromethyl)phenyl)-1H-imidazole To a stirred mixture of Intermediate 51 (1.30g, 3.90mmol) and (3R)-3- fluoropyrrolidine (0.70g, 7.81mmol) in MeOH (10mL) was added NaBH ₃ CN (0.49g, 7.81mmol) in portions at 0°C. The resulting mixture was stirred for 16h at RT then quenched with water, concentrated in vacuo and purified via RP column chromatography to afford the title compound (579mg, 36.5%) as a yellow oil. LCMS (ES+): 406.1 [MH]+. Intermediate 63 (R)-4-Bromo-1-(4-((3-fluoropyrrolidin-1-yl)methyl)-2,6-dimet hylphenyl)-1H- imidazole Intermediate 63 was prepared similarly to Intermediate 62 via reductive amination of Intermediate 52 with (R)-(-)-3-fluoropyrrolidine·HCl using NaBH3CN to afford the title compound (100mg, 77.7%) as a light-yellow solid. LCMS (ES+): 354.1 [MH]+. Intermediate 64 (R)-1-(5-(4-Bromo-1H-imidazol-1-yl)pyrazin-2-yl)-N,N-dimethy lpyrrolidin-3- amine A mixture of Intermediate 50 (400mg, 1.54mmol), DIEA (598mg, 4.62mmol) and (3R)-N,N-dimethylpyrrolidin-3-amine (176mg, 1.54mmol) in DMF (10mL) was stirred for 2h at 100°C. The resulting mixture was dried under vacuum and purified via NP column chromatography to afford the title compound (300mg, 57.7%) as a light-yellow solid. LCMS (ES+): 337.2 [MH]+. Intermediate 65 (R)-1-(5-(4-Bromo-1H-imidazol-1-yl)pyridin-2-yl)-N,N-dimethy lpyrrolidin-3- amine DIEA (3.60mL, 20.7mmol) was added to a stirred mixture of Intermediate 37 (2.50g, 10.3mmol) and (3R)-N,N-dimethylpyrrolidin-3-amine (1.97mL, 15.5mmol) in DMF (25mL) at RT, then the mixture stirred for 18h. Water (100mL) was added, and the resulting mixture extracted with EtOAc (4×100mL). The combined organic layers were washed with brine (3×10mL), dried (Na2SO4), concentrated in vacuo and purified via NP column chromatography to afford the title compound (976mg, 28.1%) as a purple solid. LCMS (ES+): 336.2 [MH]+. Intermediate 66 4-Bromo-1-(4-((1-(tert-butyl)azetidin-3-yl)oxy)phenyl)-1H-im idazole To a stirred solution of Intermediate 19 (300mg, 1.26mmol), 1-tert-butylazetidin-3- ol (243mg, 1.88mmol) and PPh ₃ (494mg, 1.88mmol) in THF (5.0mL) was added DIAD (381mg, 1.88mmol) dropwise at 0°C under N ₂ . The resulting mixture was stirred for 2h at 40°C under N ₂ then cooled to RT, quenched with water, concentrated in vacuo, and purified via NP column chromatography to afford the title compound (110mg, 25.0%) as a brown solid. LCMS (ES+): 345.0 [MH]+. Intermediates 67 to 74 Intermediates 67 to 74 were prepared similarly to Intermediate 66 via Mitsunobu reaction of Intermediates 16, 19, and 35 with the appropriate alcohol using DIAD and PPh3; see Table 5 below. Table 5: Mitsunobu reactions of Intermediates 16, 19, and 35 using DIAD and PPh ₃ ; S ; %; 0 1; ; %; 1 ; %; 5 1; %; 1 8; %; 2 8; %; 0 ; %; 3 ; %; 3 Intermediate 75 (1R,4R)-2-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-5-methyl-2,5- diazabicyclo[2.2.1]heptane Intermediate 45 (500mg, 1.66mmol), (1R,4R)-2-methyl-2,5- diazabicyclo[2.2.1]heptane (279mg, 2.48mmol), XPhos (79.0mg, 0.17mmol), XPhos Pd G3 (140mg, 0.17mmol) and Cs2CO3 (1.08g, 3.32mmol) in DXN (10mL) were stirred overnight at 100°C under N2 then cooled to RT, concentrated in vacuo and purified via NP column chromatography to afford the title compound (110mg, 19.9%) as a yellow solid. LCMS (ES+): 333.1 [MH]+. Intermediates 76 to 161 Intermediates 76 to 161 were prepared similarly to Intermediate 75 via XPhos Pd G3-catalysed Buchwald-Hartwig coupling of the specified (hetero)aryl bromide Intermediate with the appropriate amine; see Table 6 below. Table 6: XPhos Pd G3-catalysed Buchwald-Hartwig coupling of the specified (hetero)aryl bromide Intermediate with the appropriate amine S S: ; S: ; S: ; 0 S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; H]+ S: ; S: ; S: ; ; S: ; S: ; S: ; S: ; S: ; S: ; ; S: ; S: ; S: ; S: ; S: ; S: ; ; S: ; ; S: ; S: ; S: ; S: ; ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; S: ; ; S: ; S: ; S: ; S: ; ; S: ; S: ; ; ; ; Intermediates 162 and 163 tert-Butyl 6-(4-(4-bromo-1H-imidazol-1-yl)phenyl)-1,6-diazaspiro[3.4]oc tane- 1-carboxylate Intermediates 162 and 163 were prepared similarly to Intermediate 75 via XPhos Pd G3-catalysed Buchwald-Hartwig coupling of Intermediate 45 (1.76g, 5.83mmol) with tert-butyl 1,6-diazaspiro[3.4]octane-1-carboxylate hemioxalate (2.10g, 4.08mmol) then purification via NP column chromatography to afford the title compound (900mg, 35.6%) as a yellow solid. The racemic product was separated via prep-SFC Method 1to afford each enantiomer of the title compound as a single enantiomer of unknown absolute stereochemistry. Intermediate 162 (Enantiomer 1): SFC Rt 2.28min to afford the title compound (401mg, 15.9%) as a yellow solid. LCMS (ES+): 433.1 [MH]+. Intermediate 163 (Enantiomer 2): SFC Rt 4.02min to afford the title compound (430mg, 17.0%) as a yellow solid. LCMS (ES+): 433.1 [MH]+. Intermediate 164 1-(4-(4-Bromo-1H-imidazol-1-yl)-3-(trifluoromethoxy)phenyl)- 4- methylpiperazine To a stirred mixture of Intermediate 32 (500mg, 1.30mmol) and 1-methyl- piperazine (194mg, 1.94mmol) in DXN (10mL) were added tBuXPhos Pd G3 (103mg, 0.13mmol), Me ₄ tBuXPhos (60.0mg, 0.13mmol) and Cs ₂ CO ₃ (848mg, 2.60mmol) at RT under N ₂ . The mixture was heated to 100°C and stirred for 16h, filtered, and the filter cake was washed with MeOH. The filtrate was concentrated in vacuo and purified via RP column chromatography to afford the title compound (190mg, 36.2%) as a red solid. LCMS (ES+): 407.0 [MH]+. Intermediate 165 (R)-1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-N,N-dimethylpyrro lidin-3-amine Intermediate 45 (2.00g, 6.56mmol, 99.1% purity), (R)-(+)-3- (dimethylamino)pyrrolidine (1.00mL, 7.88mmol), BINAP (307mg, 0.49mmol) and NaOtBu (883mg, 9.19mmol) in PhMe (40mL) was de-gassed using N2 for 10min, then Pd ₂ dba ₃ (150mg, 0.16mmol) was added, the mixture de-gassed for a further 5min then heated to 110°C for 18h under N ₂ . The reaction mixture was diluted with DCM (100mL), filtered through Celite®, concentrated in vacuo and purified via NP column chromatography to afford the title compound (1.07g, 46.9%) as a beige solid. LCMS (ES+): 335.1 [MH]+. Intermediates 166 to 182 Intermediates 166 to 182 were prepared similarly to Intermediate 165 via Pd ₂ dba ₃ - catalysed Buchwald-Hartwig coupling of the specified aryl bromide Intermediate with the appropriate amine; see Table 7 below. Table 7: Pd2dba3-catalysed Buchwald-Hartwig coupling of the appropriate (hetero)aryl bromide Intermediate with the appropriate amine ; S S: ; S: %; S: %; S: ; S: %; S: %; S: %; S: ; S: ; S: ; S: ; S: %; S: %; S: ; S: ; S: ; 1 Intermediate 182 (R)-1-(4-(4-Bromo-1H-imidazol-1-yl)-3-(dimethylamino)phenyl) -N,N- dimethylpyrrolidin-3-amine Step 1: To a stirred mixture of Intermediate 137 (1.70g, 4.47mmol) and iron powder (2.00g, 35.8mmol) in EtOH (50mL) were added NH4Cl (1.91g, 35.8mmol) and water (403µL, 22.4mmol) at RT. The resulting mixture was stirred for 2h at 80°C then filtered and the filter cake washed with EtOH (3×20mL). The filtrate was concentrated in vacuo, then diluted with water (100mL) and extracted with EtOAc (5×100mL). The combined organic layers were washed with brine (5×20mL), dried (Na ₂ SO ₄ ), then the residue purified via NP column chromatography to afford (R)-1-(3-amino-4-(4-bromo-1H-imidazol-1-yl)phenyl)- N,N-dimethylpyrrolidin-3-amine (936mg, 59.8%) as a brown solid. LCMS (ES+): 350.3 [MH]+. Step 2: A mixture of (R)-1-(3-amino-4-(4-bromo-1H-imidazol-1-yl)phenyl)-N,N- dimethylpyrrolidin-3-amine (936mg, 2.67mmol) in MeOH (20mL) was treated with formaldehyde (2.20mL, 22.1mmol) for 10min followed by the addition of NaBH ₃ CN (336mg, 5.34mmol) at RT. The resulting mixture was stirred for 16h at 60°C, concentrated in vacuo and purified via RP column chromatography to afford the title compound (289mg, 28.6%) as a yellow solid. LCMS (ES+): 378.3 [MH]+. Intermediate 183 (R)-1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-N,N-bis(methyl-d3 )pyrrolidin-3- amine Step 1: To a solution of Intermediate 179 (243mg, 86.0% purity, 0.68mmol) and pyridine (220µL, 2.73mmol) in DCM (5.0mL) was added p-toluenesulfonyl chloride (388mg, 2.04mmol). The reaction mixture was stirred at RT for 64h then further pyridine (220µL, 2.73mmol) and p-toluenesulfonyl chloride (388mg, 2.04mmol) were added and the mixture stirred for a further 24h. The reaction mixture was concentrated in vacuo and purified via NP column chromatography to afford [(3S)-1-[4-(4-bromoimidazol-1-yl)phenyl]pyrrolidin-3-yl] 4- methylbenzenesulfonate (51.4mg, 12.8%) as a pale brown gum. LCMS (ES+): 462.1 [MH]+. Step 2: [(3S)-1-[4-(4-Bromoimidazol-1-yl)phenyl]pyrrolidin-3-yl] 4- methylbenzenesulfonate (51.4mg, 78.2% purity, 86.9µmol), K ₂ CO ₃ (60.0mg, 0.43mmol) and dimethyl-d ₆ -amine·HCl (23.0mg, 0.26mmol) in MeCN (2.0mL) were stirred at 80°C in a sealed tube for 18h. Further K ₂ CO ₃ (60.0mg, 0.43mmol) and dimethyl-d6-amine·HCl (23.0mg, 0.26mmol) were added and the mixture stirred for a further 6h at 80°C then concentrated in vacuo and purified via NP column chromatography to afford the title compound (13.8mg, 46.6%) as a pale- yellow solid. LCMS (ES+): 343.2 [MH]+. Intermediate 184 (3S,4R)-1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-4-fluoro-N- methylpyrrolidin-3-amine Step 1: A mixture of Intermediate 123 (520mg, 1.22mmol) in DMF (5.0mL) was treated with NaH (40% by weight, 73.0mg, 1.83mmol) for 30min at 0°C under N2 followed by the addition of MeI (113µL, 1.83mmol) dropwise at 0°C. The mixture was warmed to RT, stirred for 16h, quenched with water (20mL) then extracted with EtOAc (6×50mL). The combined organic layers were washed with brine (6×20mL), dried (Na2SO4), concentrated in vacuo and purified via prep- TLC (PE/EtOAc 2:1) to afford tert-butyl ((3S,4R)-1-(4-(4-bromo-1H-imidazol-1- yl)phenyl)-4-fluoropyrrolidin-3-yl)(methyl)carbamate (380mg, 70.7%) as a yellow solid. LCMS (ES+): 439.0 [MH]+. Step 2: A mixture of tert-butyl N-[(3S,4R)-1-[4-(4-bromoimidazol-1-yl)phenyl]-4- fluoropyrrolidin-3-yl]-N-methylcarbamate (380mg, 0.87mmol) and TFA (1.0mL) in DCM (10mL) was stirred for 2h at RT. The mixture was concentrated in vacuo and purified via prep-TLC (DCM / MeOH 20:1) to afford the title compound (220mg, 74.6%) as a yellow solid. LCMS (ES+): 338.9 [MH]+. Intermediate 185 tert-Butyl ((3S,4R)-1-(4-(4-bromo-1H-imidazol-1-yl)phenyl)-4- methoxypyrrolidin-3-yl)(methyl)carbamate A solution of Intermediate 149 (156mg, 0.36mmol) in DMF (3.0mL) was treated with NaH (22.0mg, 0.55mmol) for 40min at 0°C under N2 followed by the addition of MeI (33.0µL, 0.53mmol) dropwise. The resulting mixture was stirred for 1h at RT then concentrated in vacuo and purified via RP column chromatography to afford the title compound (152mg, 93.2%) as a yellow solid. LCMS (ES+): 451.0 [MH]+. Intermediate 186 tert-Butyl ((3S,4R)-1-(4-(4-bromo-1H-imidazol-1-yl)-3-methoxyphenyl)-4- fluoropyrrolidin-3-yl)(methyl)carbamate Intermediate 186 was prepared similarly to Intermediate 185 via alkylation of Intermediate 157 (220mg, 0.48mmol) with MeI (45.0µL, 0.72mmol) then purification via prep-TLC (PE/EtOAc 1:1) to afford the title compound (200mg, 88.2%) as a brown solid. LCMS (ES+): 469.1 [MH]+. Intermediate 187 tert-Butyl (R)-(1-(4-(4-bromo-1H-imidazol-1-yl)phenyl)pyrrolidin-3- yl)(ethyl)carbamate Intermediate 187 was prepared similarly to Intermediate 185 via alkylation of Intermediate 118 (200mg, 0.49mmol) with EtI (60.0µL, 0.74mmol) to afford the title compound (200mg, 93.6%) as a white solid. LCMS (ES+): 435.1 [MH]+. Intermediate 188 1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)pyrrolidin-3-one A solution of DMSO (6.50mL, 91.5mmol) in DCM (200mL) was treated with oxalyl chloride (3.90mL, 46.1mmol) for 5min at -78°C under N2 then Intermediate 181 (10.0g, 32.5mmol) in DCM (50mL) was added dropwise at -78°C. The resulting mixture was warmed to RT, stirred for 1h, then Et ₃ N (28.0mL, 202mmol) was added and the mixture stirred for 16h. DCM (200mL) was added then the reaction was quenched through addition of sat aq NaHCO3 (200mL), washed with water (6x100mL), dried (Na2SO4) and concentrated in vacuo. Purification via NP column chromatography afforded the title compound (6.00g, 60.4%) as a yellow solid. LCMS (ES+): 306.0 [MH]+. Intermediate 189 (2R,3R)-1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-N,N,2-trimeth ylpyrrolidin-3- amine Step 1: Intermediate 139 (185mg, 0.41mmol) in AcOH (4.0mL) was treated with HBr (2.0mL, 40% in AcOH) for 1h at RT then concentrated in vacuo. Purification via RP column chromatography afforded (2R,3R)-1-[4-(4-bromoimidazol-1- yl)phenyl]-2-methylpyrrolidin-3-amine (130mg, 98.8%) as a yellow solid. LCMS (ES+): 321.0 [MH]+. Step 2: A solution of (2R,3R)-1-[4-(4-bromoimidazol-1-yl)phenyl]-2- methylpyrrolidin-3-amine (130mg, 0.40mmol) in MeOH (5.0mL) was treated with formaldehyde (122µL, 1.23mmol) for 10min followed by the addition of NaBH3CN (76.0mg, 1.22mmol) at RT. The resulting mixture was stirred for 2h at RT, quenched with water (10mL), extracted with EtOAc (3×20mL) and the combined organic layers were washed with brine (3×5.0mL), dried (Na ₂ SO ₄ ) then concentrated in vacuo. Purification via prep-TLC (DCM/MeOH 10:1) afforded the title compound (90.0mg, 64.7%) as a yellow solid. LCMS (ES+) 348.9 [MH]+. Intermediate 190 (3aR,6aR)-1-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-4- methyloctahydropyrrolo[3,2-b]pyrrole Intermediate 190 was prepared similarly to Intermediate 189 via Cbz deprotection of Intermediate 144 (300mg, 0.64mmol) then reductive amination with formaldehyde using NaBH ₃ CN to afford the title compound (167mg, 75.2% over 2 steps) as a yellow solid. LCMS (ES+): 347.1 [MH]+. Intermediate 191 4-Bromo-1-(4-((((3S,4S)-4-fluoro-1-methylpyrrolidin-3- yl)oxy)methyl)phenyl)-1H-imidazole Step 1: A solution of Intermediate 56 (510mg, 1.16mmol) and TFA (2.0mL) in DCM (10mL) was stirred for 1h at RT. The resulting mixture was concentrated in vacuo to afford 4-bromo-1-(4-((((3S,4S)-4-fluoropyrrolidin-3-yl)oxy)methyl)p henyl)-1H- imidazole (390mg) as a red oil, which was used directly in the next step without further purification. LCMS (ES+): 339.9 [MH]+. Step 2: To a stirred solution of 4-bromo-1-(4-((((3S,4S)-4-fluoropyrrolidin-3- yl)oxy)methyl)phenyl)-1H-imidazole (390mg, 1.15mmol) and formaldehyde (108µL, 1.09mmol) in THF (5.0mL) was added NaBH3CN (80.0mg, 1.27mmol) at RT. The solution was stirred for 1h at RT then concentrated in vacuo and purified via RP column chromatography to afford the title compound (210mg, 51.2% over 2 steps) as a yellow oil. LCMS (ES+): 353.9 [MH]+. Intermediates 192 to 210 Intermediates 192 to 210 were prepared similarly to Intermediate 191 via Boc deprotection of the specified amine Intermediate using TFA, then reductive amination with the appropriate aldehyde or ketone using NaBH3CN, NaBH4 or STAB as the reducing agent; see Table 8 below. Table 8: Boc removal then reductive amination of the specified amine Intermediates ; S % 8 % 0 % 1 % 0 % 1 % 2 % 1 % 9 % 2 % 1 % 1 1 % 0 % 1 % 2 % 2 % 2 % 1 % 1 Intermediates 211 and 212 6-(4-(4-Bromo-1H-imidazol-1-yl)phenyl)-1-methyl-1,6-diazaspi ro[3.4]octane Intermediates 211 and 212 were prepared from Intermediates 162 and 163, respectively, similarly to Intermediate 191 via Boc deprotection of Intermediates 162 and 163 using TFA, then reductive amination with the formaldehyde using NaBH ₃ CN as the reducing agent. Intermediates 162 and 163 were isolated as single enantiomers of unknown absolute stereochemistry, therefore Intermediates 211 and 212 are also single enantiomers of absolute unknown stereochemistry. Intermediate 211 (Enantiomer 1): Isolated 80.0mg, 24.9% over 2 steps as a yellow oil. LCMS (ES+): 347.0 [MH]+. Intermediate 212 (Enantiomer 2): Isolated 150mg, 43.5% over 2 steps as a yellow oil. LCMS (ES+): 347.1 [MH]+. Intermediate 213 4-Bromo-1-(4-(3-(3,3-dimethylazetidin-1-yl)pyrrolidin-1-yl)p henyl)-1H- imidazole A mixture of Intermediate 188 (400mg, 1.31mmol), 3,3-dimethylazetidine·HCl (175mg, 1.44mmol) and STAB (831mg, 3.92mmol) in DCM (10mL) was stirred for 1h at RT. The resulting mixture was concentrated in vacuo and purified via prep- TLC (DCM/MeOH = 50:1) to afford crude product (420mg) as a yellow solid, which was further purified via prep-HPLC to afford the title compound (120mg 24.5%) as a yellow solid. LCMS (ES+): 375.1 [MH]+. Intermediate 214 4-Bromo-1-(4-(3-(3-methylazetidin-1-yl)pyrrolidin-1-yl)pheny l)-1H-imidazole Intermediate 214 was prepared similarly to Intermediate 213, via reductive amination of Intermediate 188 (400mg, 1.31mmol) with 3-methylazetidine·HCl (155mg, 1.44mmol) then purification via prep-TLC (EtOAc) to afford the title compound (200mg, 42.4%) as a yellow solid. LCMS (ES+): 361.1 [MH]+. Intermediates 215 to 226 Intermediates 215 to 226 were prepared similarly to Intermediate 213 via reductive amination of Intermediate 188 with the appropriate amine, but with a subsequent isomer separation step using either prep-SFC or chiral prep-HPLC to afford two Intermediates as either single enantiomers or single diastereomers with unknown absolute stereochemistry; see Table 9 below. Table 9: Reductive amination using Intermediate 188, then isomer separation t ; ; %; 1 ; %; 1 %; 1 %; 1 1; %; 1 1; %; 1 ; %; 1 ; %; 1 ; %; 1 ; %; 1 8; %; 1 8; %; 1 EXAMPLES Example 1 5-((1-(4-((1R,5R)-6-Methyl-3,6-diazabicyclo[3.2.0]heptan-3-y l)phenyl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile Intermediate 192 (181mg, 95.1% purity, 0.52mmol), 5-aminopyrazine-2- carbonitrile (78.0mg, 0.65mmol), Cs2CO3 (336mg, 1.03mmol), and AdBrettPhos (33.00mg, 51.5µmol) in DXN (3.0mL) was sparged with N2 for 5min, then AdBrettPhos Pd G3 (52.0mg, 51.5µmol) was added and the mixture was sparged with N ₂ for a further 5min then heated to 100°C in a sealed tube and allowed to stir for 15h. The reaction mixture was concentrated in vacuo and purified via NP column chromatography. Further purification via NH ₃ -buffered RP HPLC then drying in a vacuum oven at 60°C for 16h afforded the title compound (36.2mg, 18.6%) as a pale-yellow solid. LCMS (ES+): 373.2 [MH]+. UPLC: Rt 3.14min, 99.0% purity. Examples 2 to 104 Examples 2 to 104 were prepared similarly to Example 1 via AdBrettPhos Pd G3- catalysed Buchwald-Hartwig coupling of the specified (hetero)aryl bromide Intermediate with 5-aminopyrazine-2-carbonitrile; see Table 10 below. Table 10: AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling reactions of 5-aminopyrazine-2-carbonitrile with specified (hetero)aryl bromide ; ; ; +; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; Examples 105 to 126 Examples 105 to 126 were prepared similarly to Example 1, via AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling of the specified aryl bromide Intermediate with 5-aminopyrazine-2-carbonitrile, but with a subsequent enantiomer separation step using either prep-SFC or chiral prep-HPLC to isolate single enantiomers of unknown absolute configuration; see Table 11 below. Table 11: AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling reactions then enantiomer separation ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; Examples 127 to 140 Examples 127 to 140 were prepared similarly to Example 1 via AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling of the specified aryl bromide Intermediate with 5-aminopyrazine-2-carbonitrile. Intermediates 211-212, & 215- 226 were single enantiomers or diastereomers of unknown absolute configuration due to a prior isomer separation step using either chiral prep-HPLC or SFC, and therefore Examples 127-140 are also single enantiomers or diastereomers of unknown absolute configuration; see Table 12 below. Table 12: AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling reactions using (hetero)aryl bromide intermediates of unknown absolute configuration ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; Example 141 (R)-1-(4-(4-((5-Cyanopyrazin-2-yl)amino)-1H-imidazol-1-yl)ph enyl)-N,N- dimethylpyrrolidin-3-amine oxide To Example 12 (100mg, 0.26mmol) in DCM (8.0mL) was added mCPBA, (75% in water, 90.0mg, 0.39mmol). The mixture was stirred at RT for 30min then purified via a catch and elute cartridge. Further purification via NP column chromatography then RP HPLC afforded the title compound (15.3mg, 15.0%) as a green solid. LCMS (ES+): 391.2 [MH]+. UPLC: Rt 3.30min, 99.6% purity. Example 142 5-((1-(4-(Morpholinomethyl)phenyl)-1H-imidazol-4-yl)amino)py razine-2- carbonitrile Intermediate 15 (150mg, 0.47mmol) was reacted with 5-aminopyrazine-2- carbonitrile (83.9mg, 0.70mmol) similarly to Example 1, but using EPhos Pd G4 and Ephos instead of AdBrettPhos Pd G3 and AdBrettPhos, respectively. Purification via RP HPLC afforded the title compound (5.4mg, 3.2%) as a yellow solid. LCMS (ES+): 362.3 [MH]+. HPLC: Rt 0.91min, 98.8% purity. Examples 143 to 147 Examples 143 to 147 were prepared similarly to Example 142, via EPhos Pd G4- catalysed Buchwald-Hartwig coupling of the specified aryl bromide Intermediates with 5-aminopyrazine-2-carbonitrile; see Table 13 below. Table 13: Ephos Pd G4-catalysed Buchwald-Hartwig coupling reactions ; ; ; ; ; +; % Example 148 5-((1-(3-(3-Aminopropoxy)phenyl)-1H-imidazol-4-yl)amino)pyra zine-2- carbonitrile Step 1: Intermediate 69 (200mg, 0.51mmol) was reacted with 5-aminopyrazine-2- carbonitrile (90.9mg, 0.76mmol) similarly to Example 1 using AdBrettPhos Pd G3. Purification via RP column chromatography afforded tert-butyl N-[3-(3-{4-[(5- cyanopyrazin-2-yl)amino]imidazol-1-yl}phenoxy)propyl]carbama te (94.8mg, 43.1%) as a light brown solid. LCMS (ES+): 436.2 [MH]+. Step 2: A mixture of tert-butyl N-[3-(3-{4-[(5-cyanopyrazin-2-yl)amino]imidazol-1- yl}phenoxy)propyl]carbamate (90.0mg, 0.21mmol) and TFA (1.0mL) in DCM (5.0mL) was stirred for 30min at RT. The resulting mixture was concentrated in vacuo and purified via RP HPLC to afford the title compound (21.0mg, 28.9%) as a yellow solid. LCMS (ES+): 336.1 [MH]+. HPLC: Rt 1.02min, 95.4% purity. Examples 149 to 165 Examples 149 to 165 were prepared similarly to Example 148, via AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling of the specified aryl bromide Intermediate with 5-aminopyrazine-2-carbonitrile, then Boc deprotection using TFA; see Table 14 below. Table 14: AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling then Boc-deprotection reactions ; 2 2 ps; 2 ps; ps; ps 2 2 2 ps ps 2 rity Examples 166 and 167 5-((1-(3-(4-Amino-3,3-difluoropiperidin-1-yl)phenyl)-1H-imid azol-4- yl)amino)pyrazine-2-carbonitrile Examples 166 and 167 were prepared similarly to Example 148, via AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling of Intermediate 110 with 5- aminopyrazine-2-carbonitrile then Boc deprotection using TFA. The enantiomers were separated using chiral prep-HPLC method 10 to afford each enantiomer of the title compound as a single enantiomer of unknown absolute stereochemistry. Example 166 (Enantiomer 1): chiral prep-HPLC Rt 3.19min to afford the title compound (13.0mg, 4.7% over 2 steps) as a yellow solid. LCMS (ES+): 397.4 [MH]+. HPLC: Rt 0.74min, 99.5% purity. Example 167 (Enantiomer 2): chiral prep-HPLC Rt 4.49min to afford the title compound (11.0mg, 4.0% over 2 steps) as a yellow solid. LCMS (ES+): 397.3 [MH]+. HPLC: Rt 0.72min, 99.9% purity. Example 168 5-((1-(2-(3-Aminopropoxy)phenyl)-1H-imidazol-4-yl)amino)pyra zine-2- carbonitrile Example 168 was prepared from Intermediate 13 similarly to Example 148, but EPhos Pd G4 and Ephos were used instead of AdBrettPhos Pd G3 and AdBrettPhos, respectively, in Step 1. Purification via RP HPLC afforded the title compound (5.8mg, 19.1% over 2 steps) as a light-yellow solid. LCMS (ES+): 336.2 [MH]+. HPLC: Rt 6.26min, 97.9% purity. Example 169 (R)-5-((1-(4-((3-Fluoropyrrolidin-1-yl)methyl)-2-methoxyphen yl)-1H- imidazol-4-yl)amino)pyrazine-2-carbonitrile) Step 1: Intermediate 41 (800mg, 2.85mmol) was reacted with 5-aminopyrazine-2- carbonitrile (684mg, 5.69mmol) using AdBrettPhos Pd G3 similarly to Example 1. Purification via NP column chromatography afforded 5-[[1-(4-formyl-2-methoxy- phenyl)imidazol-4-yl]amino]pyrazine-2-carbonitrile (95.0mg, 9.6%) as a yellow solid. Step 2: 5-[[1-(4-Formyl-2-methoxy-phenyl)imidazol-4-yl]amino]pyrazin e-2- carbonitrile (20.0mg, 57.6µmol, 92.2% purity), (R)-(-)-3-fluoropyrrolidine·HCl (7.23mg, 57.6µmol) and MP-trimethylammonium cyanoborohydride resin (3.82mmol/g, 37.7mg, 0.14mmol) in IPA (0.5mL) and AcOH (50µL) was heated using a microwave reactor (100°C) for 10min. The reaction mixture was purified via a catch and elute cartridge. Further purification via RP HPLC afforded the title compound (13.9mg, 61.2%) as a yellow solid. LCMS (ES+): 394.1 [MH]+. UPLC: Rt 3.21min, 99.7% purity. Examples 170 to 174 Examples 170 to 174 were prepared similarly to Example 169 via AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling of Intermediates 41 and 42 with 5- aminopyrazine-2-carbonitrile, then reductive amination with the appropriate amine; see Table 15 below. Table 15: Buchwald-Hartwig coupling then reductive amination reactions 7; ps; ity -1; ps; ity 29- ps; ity -8; ps; ity 89- ps; ity Example 175 5-((1-(3-((2-Methyl-2-azaspiro[3.3]heptan-6-yl)oxy)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile Step 1: Intermediate 72 (60.0mg, 0.14mmol) was reacted with 5-aminopyrazine- 2-carbonitrile (24.9mg, 0.21mmol) similarly to Example 1. Purification via NP column chromatography afforded tert-butyl 6-(3-{4-[(5-cyanopyrazin-2- yl)amino]imidazol-1-yl}phenoxy)-2-azaspiro[3.3]heptane-2-car boxylate (41.2mg, 63.0%) as a light yellow solid. LCMS (ES+): 474.3 [MH]+. Step 2: A solution of tert-butyl 6-(3-{4-[(5-cyanopyrazin-2-yl)amino]imidazol-1- yl}phenoxy)-2-azaspiro[3.3]heptane-2- carboxylate (40.0mg, 0.08mmol) and TFA (1.0mL) in DCM (1.0mL) was stirred for 30min at RT. The resulting mixture was concentrated in vacuo to afford crude 5-{[1-(3-{2-azaspiro[3.3]heptan-6- yloxy}phenyl)imidazol-4-yl]amino}pyrazine-2-carbonitrile (20.0mg), which was used directly in the next step without further purification. Step 3: A solution of 5-{[1-(3-{2-azaspiro[3.3]heptan-6-yloxy}phenyl)imidazol-4- yl]amino}pyrazine-2-carbonitrile (20.0mg, 0.05mmol) and formaldehyde (5.00µL, 0.05mmol) in MeOH (1.0mL) was stirred for 30min at RT. NaBH ₃ CN (6.7mg, 0.11mmol) was added at 0°C and the resulting mixture was stirred at RT for 4h. The reaction was quenched with water, concentrated in vacuo and purified via RP HPLC (TFA-modifier) to afford the title compound as the TFA salt (2.9mg, 10.7% over 2 steps) as a yellow solid. LCMS (ES+): 388.1 [MH]+. HPLC: Rt 1.23min, 98.9% purity. Examples 176 to 180 Examples 176 to 180 were prepared similarly to Example 175, via AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling of the specified aryl bromide Intermediate with 5-aminopyrazine-2-carbonitrile, followed by TFA Boc removal, then reductive amination with the appropriate aldehyde; see Table 16 below. Table 16: AdBrettPhos Pd G3-catalysed Buchwald-Hartwig coupling then Boc removal and subsequent reductive amination reactions C -0; -0; -0; -0; rity -0; 3 Example 181 5-((1-(4-(4-(3,3-Difluorocyclobutyl)piperazin-1-yl)phenyl)-1 H-imidazol-4- yl)amino)pyrazine-2-carbonitrile Example 181 was prepared from Intermediate 20 similarly to Example 175, but EPhos Pd G4 and Ephos were used instead of AdBrettPhos Pd G3 and AdBrettPhos, respectively, in Step 1, and 3,3-difluorocyclobutan-1-one was used instead of formaldehyde in Step 3. Purification via RP HPLC afforded the title compound (4.4mg, 3.3% over 3 steps) as a light-yellow solid. LCMS (ES+): 437.0 [MH]+. HPLC: Rt 0.81min, 95.1% purity. Example 182 5-((1-(4-(4-(Oxetan-3-yl)piperazin-1-yl)phenyl)-1H-imidazol- 4- yl)amino)pyrazine-2-carbonitrile Example 182 was prepared from Intermediate 20 similarly to Example 181, but 3- oxetanone was used instead of 3,3-difluorocyclobutan-1-one in Step 3. Purification via RP HPLC afforded the title compound (2.2mg, 1.6% over 3 steps) as a yellow solid. LCMS (ES+): 403.2 [MH]+. HPLC: Rt 6.67min, 95.4% purity. Example 183 5-((1-(4-(4-(2-Fluoroethyl)piperazin-1-yl)phenyl)-1H-imidazo l-4- yl)amino)pyrazine-2-carbonitrile Step 1: Intermediate 20 (800mg, 2.85mmol) was reacted with 5-aminopyrazine-2- carbonitrile (684mg, 5.69mmol) using EPhos Pd G4 similarly to Example 142. Purification via RP HPLC afforded tert-butyl 4-(4-{4-[(5-cyanopyrazin-2- yl)amino]imidazol-1-yl}phenyl)piperazine-1-carboxylate (80.0mg, 73.0%) as a brown semi-solid. LCMS (ES)+: 447.2 [MH]+. Step 2: A solution of tert-butyl 4-(4-{4-[(5-cyanopyrazin-2-yl)amino]imidazol-1- yl}phenyl)piperazine-1-carboxylate (75.0mg, 0.17mmol) and TFA (0.5mL) in DCM (2.5mL) was stirred for 30min at RT. The resulting mixture was concentrated in vacuo to afford 5-({1-[4-(piperazin-1-yl)phenyl]imidazol-4-yl}amino)pyrazine -2- carbonitrile (40.0mg, 68.74%) as a brown semi-solid. The resulting mixture was used in the next step directly without further purification. LCMS (ES+): 347.1 [MH]+. Step 3: To a stirred solution of 5-({1-[4-(piperazin-1-yl)phenyl]imidazol-4- yl}amino)pyrazine-2-carbonitrile (40.0mg, 0.115mmol) and 1-bromo-2- fluoroethane (29.3mg, 0.23mmol) in DXN (2.0mL) were added NaI (34.6mg, 0.23mmol) and DIEA (29.8mg, 0.23mmol) at RT. The resulting mixture was stirred for 12h at 100°C, cooled to RT, filtered and the filtrate concentrated in vacuo. Purification via RP HPLC afforded the title compound (4.8mg, 10.5%) as a yellow solid. LCMS (ES+): 393.3 [MH]+. HPLC: Rt 0.69min, 99.2% purity. Examples 184 to 186 Examples 184 to 186 were prepared similarly to Example 183, via EPhos Pd G4- catalysed Buchwald-Hartwig coupling of Intermediate 20 with 5-aminopyrazine-2- carbonitrile, then Boc removal using TFA, then alkylation with the appropriate alkyl halide; see Table 17 below. Table 17: EPhos Pd G4-catlaysed Buchwald-Hartwig coupling then Boc removal then alkylation reactions lt); 3 ; 3 ; 3 ; Comparator Examples 1 to 4 Four pyrazole-NH-pyrazine-containing Chk1 inhibitors have been highlighted for comparison; see Table 18 below. Table 18: Pyrazole-NH-pyrazine-containing Comparator Examples 1 to 4 et . . 0 0 6, 0 HIGH RESOLUTION MASS SPECTROMETRY (HRMS) HRMS Method This protocol is a non-GLP UPLC-HRMS analytical method for accurate mass analysis. Samples were prepared at a concentration of 250ng/mL in water:acetonitrile (1:1) and analyzed by UPLC-HRMS using a BEH C18 50x2.1mm, 1.7μm column and 0.1% formic acid in water+0.1% acetonitrile as the mobile phase. Samples were analyzed by a Waters Synapt XS (Quadruple Time of Flight instrument) and Acquity UPLC system and corrected using LockSpray Leucine Enkephalin lockmass. The data was processed using OpenLynx application software within MassLynx. The calculated and observed mass values generated by OpenLynx are for the neutral [MH] or [M-H] or [M+H] species and the accurate mass error is reported in ppm (parts per million) and determined by the following formula: Mass Error (ppm) = ((Measured Mass – Calculated Mass) / Calculated Mass) x 10 ⁶ Table 19: HRMS Data BIOLOGICAL DATA Human Chk1 HTRF (homogeneous time resolved fluorescence) enzyme assay Method 2 μL enzyme/substrate solution (1 nM Chk-1 (Carna Bioscience # 02-177), in solution with 30 µM ATP, 4 µM STK1 S1 (Cisbio# 62ST1PEB) in assay buffer (20 mM HEPES pH7.5, 500 mM NaCl, 0.1% BGG, 1 mM DTT, 0.005% Tween-20)) and different concentrations of compounds were incubated at room temperature for 30 minutes in 384-well plates (proxiplate-384 plus, Perkin Elmer cat # 6008289). MgCl cofactor solution was added (2 μL, 20 mM) and incubation continued at room temperature for 30 minutes. 4 μL kit detection reagent (Cisbio# 62ST1PEB) was added and incubation continued for 60 minutes at room temperature. Plates were read on the PHERAstar FS using TR-FRET technology, channel A: 337/665, channel B: 337/620. % effects of a compound at a given concentration was calculated based on inhibition produced in the DMSO control wells and inhibited control wells control wells in each assay plate. Compound IC s were determined with a four-parameter logistic dose response equation using 11 point dose response curves, analysing within the Dotmatics platform. The exemplified compounds of the invention were tested for their inhibitory potential of human Chk1 kinase in the HTRF assay and the pIC50 data is shown in Table 20. pIC ₅₀ is the negative log of the IC ₅₀ value when converted to molar. All of the exemplified compounds of the invention have a pIC ₅₀ value >6. This data shows that the compounds of the invention can inhibit Chk1. Table 20: Chk1 pIC50 data (A: 6-6.5, B: 6.5-7.0, C: 7.0-7.5, D: 7.5-8.0, E: ≥8.0) Cancer cell line data In vitro cell viability assay GBM LN18 cells were incubated with increasing concentrations of selected compounds of the invention for 72 hours prior to the measurement of ATP in metabolically viable cells with the Cell Titre® Glo Luminescent reagent. A 10-point concentration response curve up to a maximum concentration of 10 μM was tested. The percent (%) effect i.e., inhibition at each concentration of compound was calculated based on, and relative to the amount of inhibition produced in the vehicle control and inhibited control wells contained within each plate. The log molar concentrations and % inhibition values were plotted and the concentration of compound required for 50% inhibition (IC50) was determined using the four- parameter logistic dose response equation. ELISA Cell-based on-target kinase activity was measured for selected compounds of the invention using a sandwich ELISA assay kit (pChk1 PathScan ELISA kit, Cell Signalling Technologies, Cat #7870) with pChk1(Ser296) as the detection antibody. SW620 cells were seeded in 96-well plates and incubated overnight at 37oC, 5% CO2 prior to being treated with the DNA damage-inducer neocarzinostatin (7.5μM) and increasing concentrations of test agent. Cells were returned to the incubator for 2 hours and thereafter lysed in 30 μl of the lysis buffer provided in the kit (1:10 dilution of 10x cell lysis buffer #9803 supplemented with protease and phosphatase inhibitors). ELISA assays were performed as per the manufacturer's protocol. However, an alternative detection antibody pChk1(Ser296; Cat #2349, Cell Signalling Technology) was used instead of the pChk1(Ser317) antibody supplied with the kit. Selected compounds of the invention were tested as a 8- point concentration response up to a maximum concentration of either 1μM, 3μM or 10μM. The percent (%) effect i.e. inhibition at each concentration of compound was calculated based on, and relative to, the amount of inhibition produced in the vehicle control and inhibited control wells contained within each plate. The concentrations and % inhibition values for tested compounds were plotted on a dose response curve and the concentration of compound required for 50% inhibition (IC ₅₀ ) was determined with a four-parameter logistic dose response equation. A selection of the exemplified compounds of the invention were tested for their inhibitory potential in the human-derived glioblastoma (LN18) and colorectal cancer (SW620) cell lines, and the data is shown in Table 21. pIC50 is the negative log of the IC50 value when converted to molar. These data show that the compounds of the invention are effective in cancer cell lines at therapeutically relevant concentrations. Table 21: Cellular pIC ₅₀ data (A: 5.0-6.0, B: >6.0) 50 Kinome selectivity Selected compounds of the invention were tested for wider kinome selectivity against the Eurofins KinaseProfiler™ kinase screen consisting of 373 human wild- type kinases, using a 9-point concentration response curve up to a top concentration of 10µM. The radiometric kinase activity assays were run at approximately the ATP Km for each kinase. The number of kinases inhibited within 10-fold and 100-fold Chk1 IC50 are shown in Table 22, which indicates that these compounds have excellent selectivity for Chk1 over the wider kinome. Table 22: Selectivity for Chk1 within a panel of 373 human wild-type kinases Human Chk2 HTRF enzyme assay Method 2 μL enzyme/substrate solution (2 nM Chk-1 (Carna Bioscience # 02-162), in solution with 200 µM ATP, 4 µM STK1 S1 (Cisbio# 62ST1PEB) in assay buffer (20 mM HEPES pH7.5, 500 mM NaCl, 0.1% BGG, 1 mM DTT, 0.005% Tween-20)) and different concentrations of compounds were incubated at room temperature for 30 minutes in 384-well plates (Proxiplate-384 plus, Perkin Elmer cat # 6008289). MgCl cofactor solution was added (2 μL, 20 mM) and incubation continued at room temperature for 30 minutes. 4 μL kit detection reagent (Cisbio# 62ST1PEB) was added and incubation continued for 60 minutes at room temperature. Plates were read on the PHERAstar FS using TR-FRET technology, channel A: 337/665, channel B: 337/620. % effects of a compound at a given concentration was calculated based on inhibition produced in the DMSO control wells and inhibited control wells control wells in each assay plate. Compound IC s were determined with a four-parameter logistic dose response equation, using 11 point dose response curves, analysing within the Dotmatics platform. The exemplified compounds of the invention were tested for their inhibitory potential of human Chk2 kinase in the HTRF assay and the pIC ₅₀ data is shown in Table 23. All of the exemplified compounds of the invention have a pIC ₅₀ value <6. This data shows that the compounds of the invention are not potent Chk2 inhibitors. Table 23: Chk2 pIC50 data (A: ≤4.0, B: 5.0-4.0, C: 6.0-5.0) RSK1-4 kinase assay Selected compounds of the invention were tested for their inhibitory potential of RSK1, RSK2, RSK3 and RSK4 kinases via the Eurofins KinaseProfiler™ service, using a 9-point concentration response curve up to a top concentration of 10µM. The radiometric kinase activity assays were run at approximately the ATP K _m for each kinase and the IC ₅₀ data is shown in Table 24. This data shows that the compounds of the invention are not potent RSK1-4 inhibitors. Table 24: RSK1-4 IC50 data (nM) 0 MDCK-MDR1 and MDCK-BCRP efflux assay Assay protocol: Wild-type (WT) MDCK, MDR1-MDCK and BCRP-MDCK cells were seeded into 24 well Transwell plates and cultured for 3days to form monolayers. Test compounds were prepared at 1μM in Hanks’ Balanced Salt Solution containing 25mM HEPES and loaded into the donor compartments of Transwell plates bearing the cell monolayers (pH 7.4 for both donor and receiver compartments). Lucifer Yellow was added to the apical buffer in all wells to assess integrity of the cell monolayer. Duplicate wells were prepared and incubated at 37°C in a CO ₂ incubator. Samples were removed at time 0 and 60min and test compound analysed by LC-MS/MS. Concentrations of Lucifer Yellow in the samples were measured using a fluorescence plate reader. The apparent permeability (Papp) values of test compound were determined for both the apical to basal (A>B) and basal to apical (B>A) permeation and the efflux ratio (B>A:A>B) determined in each cell line. Compounds that can freely permeate the blood-brain barrier (BBB) typically have ≤1 hydrogen bond donors, tPSA ≤90Å2 (Hitchcock, J Med Chem, 2012, 4877- 4895), high passive permeability with apparent permeability (Papp) values >15x10e-6 cm/s, and low efflux by P-glycoprotein (P-gp), encoded by the MDR1 gene, and BCRP with efflux ratios ≤2.5 (Doan et al., J Pharmacol Exp Ther, 2002, 1029-1037). The data in Table 25 suggests that many of the compounds of the invention may be able to efficiently cross the blood-brain barrier to treat cancers of the brain and central nervous system. Table 25: CNS-relevant properties of selected Examples o Determination of CNS penetration in vivo Male Sprague Dawley Rats 300–350g (Charles River, UK) were group housed, n=2, under a 12h light/dark cycle with food and water available ad libitum. Two days prior to dosing, animals were anaesthetised with inhaled isoflurane, and the right jugular vein was exposed and surgically cannulated. Animals were then housed singly for recovery, and throughout the remaining procedure. On the day of dosing animals were weighed, tail marked and dosed intravenously via the indwelling cannula with compound at 0.25mg/kg in a volume of 3mL/kg. Animals were culled at 15min post dose via intravenous administration of pentobarbital. Post-mortem blood was withdrawn via cardiac puncture, and briefly stored in K2 EDTA blood tubes on ice before being spun at 14,000g for 4min at 4°C. Plasma was withdrawn into a 96 well plate, placed on dry ice and stored at -80°C. Brains were quickly dissected and placed on dry ice before storage at -80°C. Following dosing of test compound (intravenous) to Male Sprague-Dawley Rats, animals are sacrificed at 15min timepoint. Plasma is isolated from whole blood following cardiac exsanguination by centrifugal blood fractionation and whole brains isolated. Samples are stored on-ice and transferred to the Bioanalytical lab storage at -80°C. Bioanalysis of plasma and brain samples is performed as detailed below. Plasma Bioanalysis Typically, a 1.00mg/mL DMSO stock was used to prepare calibration standards of test compound in the range 1.00 to 6,000ng/mL. Calibration lines were prepared by printing known masses of analyte into a 96-well plate in the range 25 to 150,000pg. A volume of 25µL of control male Sprague-Dawley Rat plasma was added to each well to prepare calibration standards at the appropriate concentration across the calibration range. Experimental samples were thawed to room temperature and 25µL aliquots were added to the 96-well precipitation plate alongside the calibration lines. Samples were extracted using protein precipitation (agitation for at least 5min at RT with 300µL of MeCN containing 25ng/mL tolbutamide as an internal standard). Protein precipitates were separated from the extracted test compound by centrifugation at 4000rpm for 5min, 4°C. The resulting supernatants were diluted in a ratio of 1:2 with diluent, 1:1 MeOH:H ₂ O. Samples were analysed by UPLC-MS/MS on either an AB Sciex API6500 QTrap or Waters TQ-S mass spectrometer using previously optimised analytical MRM (multiple reaction monitoring) methods, specific to the test compound. The concentration of test compound in isolated samples was determined following analysis of the samples against the two replicates of the calibration line, injected before and after the sample set with an appropriate regression and weighting used. Only calibrators within ± 15% of the expected test concentration value were included in the calibration line (± 20% at the LLoQ) and any samples that fell outside of the limits of the calibration line were deemed to be less than or above the limit of quantification (LLoQ/ALoQ). Brain Bioanalysis Typically, a 1.00mg/mL DMSO stock was used to prepare calibration standards of test compound in the range 3.00 to 18,000 ng/mL. Calibration lines were prepared by printing known masses of analyte into a 96-well plate in the range 25 to 150,000 pg. A volume of 25µL of control male Sprague-Dawley Rat brain homogenate (containing 8.33mg of brain tissue) was added to each well to prepare calibration standards at the appropriate concentration across the calibration range. To prepare control and experimental brain homogenates, brains were thawed at room temperature, weighed and a volume of diluent added (50:50 MeCN/H2O) in the ratio of 2mL per gram of brain. Homogenisation of brains was performed by bead-beater homogenisation using Precellys Evolution and CKMix507mL mixed ceramic bead homogenisation tubes. Aliquots of 25µL experimental sample were extracted alongside the calibration lines using protein precipitation (agitation for at least 5 min at room temperature with 300µL of MeCN containing 25ng/mL tolbutamide as an internal standard).Protein precipitates were separated from the extracted test compound by centrifugation at 4000rpm for 5min, 4°C. The resulting supernatants were diluted in a ratio of 1:2 with diluent, 1:1 MeOH:H ₂ O. Samples were analysed by UPLC-MS/MS on either an AB Sciex API6500 QTrap or Waters TQ-S mass spectrometer using previously optimised analytical MRM (multiple reaction monitoring) methods, specific to the test compound. The concentration of test compound in isolated samples was determined following analysis of the samples against the two replicates of the calibration line, injected before and after the sample set with an appropriate regression and weighting used.Only calibrators within ± 15% of the expected test concentration value (±20% at the LLoQ) were included in the calibration line and any samples that fell outside of the limits of the calibration line were deemed to be less than or above the limit of quantification (LLoQ/ALoQ). Determination of Unbound Brain to Plasma Ratio The free drug hypothesis states that only unbound compound is able to interact with and elicit a pharmacological effect. Therefore, it is desirable for compounds to have a high free brain concentration. To calculate the free concentrations in each matrix, the determined concentrations are multiplied by the % free value as determined by plasma protein binding and brain tissue binding studies using rapid equilibrium dialysis. The Kpuu is calculated as the ratio of free drug fraction unbound in brain to free drug unbound in plasma. The results (Table 26) show that the compounds of the invention have a high free brain concentration (K _puu ). That is, they have a higher ratio of free drug fraction unbound in brain to free drug unbound in plasma. This makes them better able to elicit a pharmacological effect in the brain. Table 26: Unbound Brain to plasma partitioning (Kpuu) for selected compounds _uu 2 5 8 4