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Title:
HYDRAZINECARBOTHIOAMIDE AND 1,2,4-TRIAZOLE-3-THION DERIVATIVE COMPOUNDS CARRYING IMIDAZO[2,1-b]THIAZOLE RING AND SYNTHESIS METHODS OF THESE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2024/076331
Kind Code:
A1
Abstract:
In the invention, hydrazinecarbotioamide and 1,2,4-triazole-3-thion derivative compounds carrying an imidazo[2,1-b]thiazole ring, which have an inhibition activity on the alpha glucosidase (α-glucosidase) enzyme, and the synthesis methods of these compounds are described. The general structure of the molecules of the invention is shown by Formula (X).

Inventors:
GUZELDEMIRCI NURAY (TR)
DINCEL EFE DOGUKAN (TR)
YILMAZ OZDEN TUGBA (TR)
HASBAL CELIKOK GOZDE (TR)
Application Number:
PCT/TR2023/051076
Publication Date:
April 11, 2024
Filing Date:
October 04, 2023
Export Citation:
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Assignee:
ISTANBUL UNIV REKTORLUGU (TR)
International Classes:
A61K31/4164; A61K31/15; A61K31/4188; A61K31/4196; A61P3/10
Domestic Patent References:
WO2008058641A12008-05-22
Other References:
DINCEL EFE DOğUKAN; HASBAL-CELIKOK GOZDE; YILMAZ-OZDEN TUGBA; ULUSOY-GüZELDEMIRCI NURAY: "Design, biological evaluation, molecular docking study and in silico ADME prediction of novel imidazo[2,1-b]thiazole derivatives as a novel class of α-glucosidase inhibitors", JOURNAL OF MOLECULAR STRUCTURE, ELSEVIER AMSTERDAM, NL, vol. 1245, 7 August 2021 (2021-08-07), NL , XP086791685, ISSN: 0022-2860, DOI: 10.1016/j.molstruc.2021.131260
NURAY ULUSOY GÜZELDEMİRCİ: "Synthesis and Aldose Reductase Inhibitory Effect of Some New Hydrazinecarbothioamides and 4-Thiazolidinones Bearing an Imidazo[2,1-b]Thiazole Moiety", TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 16, no. 1, 1 March 2019 (2019-03-01), pages 1 - 7, XP093159142, ISSN: 1304-530X, DOI: 10.4274/tjps.05900
Attorney, Agent or Firm:
TEKE KARSLI, Gizem (TR)
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Claims:
CLAIMS 1. - glucosidase) represented by formula X, Formula X wherein R is selected from the formulas below: 2. A compound according to claim 1, wherein, in the case that R= , it is shown by Formula 1a-e,

Formula 1a-e wherein R is selected from the formulas below: 3. A compound according to claim 2 having any of the following formulas: 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N- allylhydrazine-1-carbotioamide (Formula 1a) 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N- benzylhydrazine-1-carbotioamide (Formula 1b) 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N- phenethylhydrazine-1-carbotioamide (Formula 1c) 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4- nitrophenyl)hydrazine-1-carbotioamide (Formula 1d) 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide (Formula 1e). 4. Compound according to Claims 2 or 3, wherein, in the case that R is selected as Formula a, 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N- allylhydrazine-1-carbotioamide compound (Formula 1a) is obtained.

5. A compound according to Claim 4, wherein the melting temperature of 2-[2-(6- (4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-allylhydrazine-1- carbotioamide compound (Formula 1a) is 228-229oC. 6. A compound according to Claim 4, wherein 2-[2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl]-N-allylhydrazine-1-carbotioamide compound (Formula 1a) comprises C, 52.37; H, 4.25; N, 17.91, by mass (%). 7. Compound according to Claim 4, wherein IR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-allylhydrazine-1- carbotioamide compound (Formula 1a) comprises ): 3221, 3138 (N-H stretching bands), 3061 (aromatic C-H stretching band), 2978, 2885 (aliphatic asymmetric and symmetric C-H stretching bands), 1674 (amide I, C=O stretching band), 1606, 1548, 1492, 1463 (amide II and aromatic C=N and C=C stretching bands), 1406, 1381 (aliphatic asymmetric and symmetric C-H bending bands), 1301, 1240 (amide III N-H bending and C-N stretching bands), 1215 (C=S stretching band), 1157 (ar. C-F stretch band), 852 (aromatic 1,4- disubstitution) peaks. 8. A compound according to Claim 4, wherein 1H NMR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-allylhydrazine-1- carbotioamide compound (Formula 1a) comprises 1H NMR (500 MHz) (DMSO- d6 2CONH), 4,16 (s, 2H, N-CH2-CH=CH2), 5,04, 5,06 (dd, J = 10,3 ; 1,8 Hz, 1H, CH=CH2, cis), 5,14, 5,17 (dd, J = 17,2 ; 1,8 Hz, 1H, CH = CH2, trans), 5,80-5,92 (m, 1H, CH=CH2), 7,10 (s, 1H, imid.tiy. C2-H), 7,25 (t, J = 8.9 Hz, 2H, 4-FPh C3,5-H), 7,84 ; 7,86 (dd, J = 8,8 ; 3,2 Hz, 2H, 4- FPh C2,6-H), 8,15 (s, 1H, imid.tiy. C5-H), 8,34 (s, 1H, NH), 9,40 (s, 1H, NH), 10,21 (s, 1H, NH) peaks. 9. A compound according to Claim 4, wherein 13C-NMR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-allylhydrazine-1- carbotioamide compound (Formula 1a) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 2CONH), 46,36 (CH2-CH=CH2), 108,88 (imid.tiy. C5), 110,90 (imid.tiy. C2), 115,72 (CH=CH2), 115,88 ; 116,05 (4-FPh C3,5), 126,60 (imid.tiy. C3), 126,92 ; 126,98 (4-FPh C2,6), 131,28 ; 131,30 (4-FPh C1), 135,29 (CH=CH2), 145,49 (imid.tiy. C6), 149,10 (imid.tiy. C7a), 160,85 ; 162,79 (Ph C4), 167,20 (CONH), 171,57 (C=S) peaks.

10. A compound according to Claims 2 or 3, wherein, in the case that R is selected as Formula 1b, 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N- benzylhydrazine-1-carbotioamide compound (Formula 1b) is obtained. 11. A compound according to Claim 10, wherein the melting temperature of 2-[2-(6- (4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1- carbotioamide compound (Formula 1b) is 245-246oC. 12. A compound according to Claim 10, wherein 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1- carbotioamide compound (Formula 1b) comprises C, 57.08; H, 4.22; N, 16.02, by mass (%). 13. A compound according to Claim 10, wherein IR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1- carbotioamide compound (Formula 1b) comprises ): 3240, 3149 (N-H stretching band), 3064 (aromatic C-H stretching band), 2972, 2883 (aliphatic asymmetric and symmetric C-H stretching bands), 1672 (amide I, C=O stretching band), 1587, 1548, 1489, 1463 (amide II and aromatic C=N and C=C stretching bands), 1409, 1381 (aliphatic asymmetric and symmetric C-H bending bands), 1300, 1261 (amide III N-H bending and C-N stretching bands), 1215 (C=S stretching band), 1151 (ar. C-F stretch band), 848 (aromatic 1,4- disubstitution), 731, 692 (aromatic monosubstitution) peaks. 14. A compound according to Claim 10, wherein 1H NMR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1- carbotioamide compound (Formula 1b) comprises 1H NMR (500 MHz) (DMSO- d6 3,84 (s, 2H, CH2CONH), 4,78 (d, J = 5,9 Hz, 2H, NH-CH2- C6H5), 7,09 (s, 1H, imid.tiy. C2-H), 7,17-7,41 (m, 7H, 4-FPh C3,5-H and benzyl), 7,79, 7,81 (dd, J = 8,8 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,13 (s, 1H, imid.tiy. C5-H), 8,70 (s, 1H, NH), 9,47 (s, 1H, NH), 10,26 (s, 1H, NH) peaks. 15. A compound according to Claim 10, wherein 13C-NMR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1- carbotioamide compound (Formula 1b) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 2CONH), 47,19 (NHCH2), 108,86 (imid.tiy. C5), 110,89 (imid.tiy. C2), 115,87 ; 116,04 (4-FPh C3,5), 126,59 (imid.tiy. C3), 126,92 ; 126,99 (4-FPh C2,6), 127,12 (benzylic Ph C4), 127,38 (benzylic Ph C2,6), 128,55 (benzylic Ph C3,5), 131,26 ; 131,29 (4-F Ph C1), 139,64 (benzylic Ph C1), 145,43 ; 145,51 (imid. tiy. C6), 149,10 (imid. tiy. C7a), 160,83 ; 162,77 (4-FPh C4), 167,29 (CONH), 171,50 (C=S) peaks. 16. A compound according to Claims 2 or 3, wherein, in the case that R is selected as Formula 1c, 2-[2-(6-(4-Fluorophenyl)imidazo[2,1- c]thiazol-3-yl)acetyl]-N- phenethylhydrazine-1-carbotioamide compound (Formula 1c) is obtained. 17. A compound according to Claim 16, wherein, the melting temperature of 2-[2-(6- (4-Fluorophenyl)imidazo[2,1- c]thiazol-3-yl)acetyl]-N-phenethylhydrazine-1- carbotioamide compound (Formula 1c) is 220-221oC. 18. A compound according to Claim 16, wherein, the temperature of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1- c]thiazol-3-yl)acetyl]-N-phenethylhydrazine-1- carbotioamide compound (Formula 1c) comprises C, 58,26; H, 4,59; N, 15,50%, by mass (%). 19. A compound according to Claim 16, wherein IR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1- c]thiazol-3-yl)acetyl]-N-phenethylhydrazine-1- ): 3248, 3142 (N-H stretching bands), 3076 (aromatic C-H stretching band), 2962, 2875 (aliphatic asymmetric and symmetric C-H stretching bands), 1672 (amide I, C=O stretching band), 1600, 1546, 1490, 1463 (amide II and aromatic C=N and C=C stretching bands), 1415, 1350 (aliphatic asymmetric and symmetric C-H bending bands), 1292, 1285 (amide III N-H bending and C-N stretching band), 1213 (C=S stretching band), 1149 (ar. C-F stretch band), 846 (aromatic 1,4-disubstitution), 731, 694 (aromatic monosubstitution) peaks. 20. A compound according to Claim 16, wherein 1H NMR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1- c]thiazol-3-yl)acetyl]-N-phenethylhydrazine-1- carbotioamide compound (Formula 1c) comprises 1H NMR (500 MHz) (DMSO- d6 J = 8,0 Hz, 2H, NHCH2CH2Ph), 3,64-3,79 (m, 2H, NHCH2CH2Ph), 3,86 (s, 2H, CH2CONH), 7,11 (s, 1H, imid.tiy. C2-H), 7,17-7,29 (m.5H, -CH2CH2C6H5), 7,31 (t, J = 7,5 Hz, 2H, 4-FPh C3,5-H), 7,86, 7,88 (dd, J = 8,6 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,21 (s, 1H, imid.tiy. C5-H), 8,28 (s, 1H, NH), 9,40 (s, 1H, NH), 10,23 (s, 1H, NH) peaks. 21. A compound according to Claim 16, wherein 13C-NMR spectrum of 2-[2-(6-(4- Fluorophenyl)imidazo[2,1- c]thiazol-3-yl)acetyl]-N-phenethylhydrazine-1- carbotioamide compound (Formula 1c) comprises 13C-NMR (APT) (125 MHz) (DMSO- 2CONH), 35,43 (NHCH2CH2Ph), 45,80 (NHCH2CH2Ph), 108,86 (imid.tiy. C5), 110,94 (imid.tiy. C2), 115,89 ; 116,06 (4- FPh C3,5), 126,58 (imid.tiy. C3), 126,65 (phenethyl Ph C4), 126,93, 126,99 (4- FPh C2,6), 128,79, 128,89 (phenethyl Ph C2,6), 129,06; 129,12 (phenethyl Ph C3,5), 131,30; 131,32 (4-FPh C1), 139,61 (phenethyl Ph C1), 145,43; 145,55 (imid.tiy. C6), 149,14 (imid.tiy. C7a), 160,85 ; 162,79 (4-FPh C4), 167,18 (CONH), 171,67 (C=S) peaks. 22. A compound according to Claims 2 or 3, wherein, in the case that R is selected as Formula d, 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4- nitrophenyl)hydrazine-1-carbotioamide compound (Formula 1d) is obtained. 23. A compound according to Claim 22, wherein, the melting temperature of 2-(2-(6- (4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitrophenyl)hydrazine- 1-carbotioamide compound (Formula 1d) is 214-215oC. 24. A compound according to Claim 22, wherein, the 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitrophenyl)hydrazine-1- carbotioamide compound (Formula 1d) comprises C, 50,26; H, 3,31; N, 17,92, by mass (%). 25. A compound according to Claim 22, wherein IR spectrum of 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitrophenyl)hydrazine-1- ): 3286, 3119 (N-H stretching bands), 3095 (aromatic C-H stretching band), 2902, 2846 (aliphatic asymmetric and symmetric C-H stretching bands), 1681 (amide I C=O stretching band), 1596, 1325 (NO2 stretching bands), 1603, 1533, 1509, 1441 (amide II and aromatic C=N and C=C stretching bands), 1415, 1369 (aliphatic asymmetric and symmetric C-H bending bands), 1299, 1262 (amide III N-H bending and C-N stretching bands), 1217 (C=S stretching band), 1154 (ar. C-F stretch band), 835, 817 (aromatic 1,4-disubstitution) peaks. 26. A compound according to Claim 22, wherein 1H NMR spectrum of 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitrophenyl)hydrazine-1- carbotioamide compound (Formula 1d) comprises 1H NMR (500 MHz) (DMSO- d6 2CONH), 7,15 (s, 1H, imid.tiy. C2-H), 7,24 (t, J = 8,7 Hz, 2H, 4-FPh C3,5-H), 7,73-7,87 (m, 2H, 4-FPh C2,6-H), 7,93 (d, J = 7,7 Hz, 2H, 4-NO2Ph C2,6-H), 8,05-8,41 (m, 3H, imid.tiy. C5-H and 4-NO2Ph C3,5-H), 10,15 (s, 1H, NH), 10,51 (s, 1H, NH), 10,89 (s, 1H, NH) peaks.

27. A compound according to Claim 22, wherein 13C-NMR spectrum of 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitrophenyl)hydrazine-1- carbotioamide compound (Formula 1d) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 2CONH), 108,83 (imid.tiy. C5), 111,23 (imid.tiy. C2), 115,91 ; 116,08 (4-FPh C3,5), 117,01 (4-NO2Ph C2,6), 125,99 (4- NO2Ph C3,5), 126,48 (imid.tiy. C3), 126,91 ; 126,98 (4-FPh C2,6), 131,09 ; 131,11 (4-FPh C1), 145,38 (imid.tiy. C6), 147,06 (4-NO2Ph C1), 149,12 (imid.tiy. C7a), 156,45 (4-NO2Ph C4), 160,88 ; 162,82 (4-FPh C4), 166,94 (CONH), 171,52 (C=S) peaks. 28. A compound according to Claims 2 or 3, wherein, in the case that R is selected as Formula e, 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide compound (Formula 1e) is obtained. 29. A compound according to Claim 28, wherein, the melting temperature of 2-(2-(6- (4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide compound (Formula 1e) is 207- 208oC. 30. A compound according to Claim 28, wherein, the 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide compound (Formula 1e) comprises C, 47,42; H, 2,93; N, 13,90, by mass (%). 31. A compound according to Claim 28, wherein IR spectrum of 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide compound (Formula 1e) comprises ): 3208 (N-H stretching band), 3098, 3057 (aromatic C-H stretching bands), 2965, 2895 (aliphatic asymmetric and symmetric C-H stretching bands), 1678 (amide I, C=O stretching band), 1597, 1546, 1494, 1463 (amide II and aromatic C=N and C=C stretching bands), 1406, 1384 (aliphatic asymmetric and symmetric C-H bending bands), 1285, 1260 (amide III N-H bending and C-N stretching bands), 1224 (C=S stretching band), 1154 (ar. C-F stretch band), 866, 808 (aromatic 1,2,4-trisubstitution), 848 (aromatic 1,4- disubstitution), 739 (ar. C-Cl stretch band) peaks. 32. A compound according to Claim 28, wherein 1H NMR spectrum of 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide compound (Formula 1e) comprises 1H NMR (500 MHz) (DMSO-d6 3,90 (s, 2H, CH2CONH), 7,16 (s, 1H, imid.tiy. C2-H), 7,24 (t, J = 8,8 Hz, 2H, 4-FPh C3,5-H), 7,34-7,42 (m, 1H, 2,4- diClPh C3-H), 7,43, 7,45 (dd, J = 8,5 ; 2,4 Hz, 1H, 2,4-diClPh C5-H), 7,68-7,73 (m, 1H, 2,4-diClPh C6-H), 7,80, 7,81 (dd, J = 8,7 ; 3,0 Hz, 2H, 4FPh C2,6-H), 8,19 (s, 1H, imid.tiy. C5-H), 9,70 (s, 1H, NH), 9,94 (s, 1H, NH), 10,49 (s, 1H, NH) peaks. 33. A compound according to Claim 28, wherein 13C-NM spectrum of 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4- dichlorophenyl)hydrazine-1-carbotioamide compound (Formula 1e) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 33,05 (CH2CONH), 109,10 (imid.tiy. C5), 111,48 (imid.tiy. C2), 115,97 ; 116,15 (4-FPh C3,5), 126,72 (imid.tiy. C3), 127,00 ; 127,07 (4-FPh C2,6), 127,91 (2,4-diClPh C6), 129,39 (2,4-diClPh C5), 132,91 (2,4 diClPh C3), 130,67 (2,4-diClPh C2), 132,25 (4-FPh C1), 133,29 (2,4-diClPh C4), 136,42 (2,4-diClPh C1), 144,79 (imid.tiy. C6), 148,99 (imid.tiy. C7a), 160,96 ; 162,89 (4-FPh C4), 167,27 (CONH), 171,60 (C=S) peaks. 34. A compound according to claim 1, wherein, in the case that R= Formula 2a-e

35. A compound according to claim 34 having any of the following formulas: 4-Allyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazol-3-thion (Formula 2a) 4-Benzyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazol-3-thion (Formula 2b) 4-Phenethyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)- 2,4-dihydro-3H-1,2,4-triazol-3-thion (Formula 2c) 4-(4-Nitrophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3- yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thion (Formula 2d) 4-(2,4-Dichlorophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3- yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thion (Formula 2e) 36. A compound according to Claims 34 or 35, wherein, in the case that R is selected as Formula a, 4-Allyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)- 2,4-dihydro-3H-1,2,4-triazol-3-thion compound (Formula 2a) is obtained. 37. A compound according to Claim 36, wherein, the melting temperature of 4-Allyl- 5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazol-3-thion compound (Formula 2a) is 277-278oC. 38. A compound according to Claim 36, wherein, the 4-Allyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3- thion compound (Formula 2a) comprises C, 54,66; H, 3,89; N, 18,42, by mass (%). 39. A compound according to Claim 36, wherein IR spectrum of 4-Allyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3- ): 3412, 3108 (N- H stretching bands), 3078, 3016 (aromatic C-H stretching bands), 2980, 2891 (aliphatic asymmetric and symmetric C-H stretching bands), 1596, 1548, 1532, 1452 (aromatic C=N and C=C stretching bands), 1412, 1345 (aliphatic asymmetric and symmetric C-H bending bands), 1287, 1237 (C-N stretching bands), 1221 (C=S stretching band), 1147 (ar. C-F stretch band), 835 (aromatic 1,4-disubstitution) peaks. 40. A compound according to Claim 36, wherein 1H NMR spectrum of 4-Allyl-5-((6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol- 3-thion compound (Formula 2a) comprises 1H NMR (500 MHz) (DMSO-d6/TMS) 4,44 (s, 2H, imid.tiy. C3-CH2), 4,77 (d, J = 6,2 Hz, 2H, N-CH2-CH=CH2), 5,07, 5,11 (dd, J = 17,2, 1,5 Hz, 1H CH = CH2, trans), 5,18, 5,20 (dd, J = 10,4, 1,5 Hz, 1H, CH=CH2, cis), 5,85 5,95 (m, 1H, CH=CH2), 7,29 (t, J = 8,8 Hz, 2H, 4-FPh C3,5-H), 7,35 (s, 1H, imid.tiy. C2-H), 7,87 ; 7,89 (dd, J = 8,7 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,33 (s, 1H, imid.tiy. C5-H), 13,77 (s, 1H, NH) peaks. 41. A compound according to Claim 36, wherein 13C-NMR spectrum of 4-Allyl-5-((6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol- 3-thion compound (Formula 2a) comprises 13C-NMR (APT) (125 MHz) (DMSO- d6 : 24,48 (imid.tiy. C3-CH2), 45,63 (triazole NCH2CH=CH2), 109,50 (imid.tiy. C5), 113,40 (imid.tiy. C2), 116,18 ; 116,36 (4-FPh C3,5), 118,20 (triazole NCH2CH=CH2), 126,16 (imid.tiy. C3), 127,35; 127,41 (4-FPh C2,6), 129,02 (4-FPh C1), 131,72 (triazole NCH2CH=CH2), 142,96 (imid.tiy. C6), 148,11 (imid.tiy. C7a), 148,72 (triazole C=N), 161,25 ; 163,20 (4-FPh C4), 167,66 (C=S) peaks. 42. A compound according to Claims 34 or 35, wherein, in the case that R is selected as Formula b, 4-Benzyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)- 2,4-dihydro-3H-1,2,4-triazol-3-thion compound (Formula 2b) is obtained. 43. A compound according to Claim 42, wherein, the melting temperature of 4- Benzyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H- 1,2,4-triazol-3-thion compound (Formula 2b) is 273-274oC. 44. A compound according to Claim 42, wherein, the 4-Benzyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3- thion compound (Formula 2b) comprises C, 58,76; H, 4,85; N, 14.67%, by mass (%).

45. A compound according to Claim 42, wherein, the IR spectrum of 4-Benzyl-5-((6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol- 3-thion compound (Formula 2b) comprises ): 3134 (N-H stretching band), 3098, 3020 (aromatic C-H stretching bands), 2916, 2878 (aliphatic asymmetric and symmetric C-H stretching bands), 1594, 1564, 1512, 1450 (aromatic C=N and C=C stretching bands), 1419, 1374 (aliphatic asymmetric and symmetric C-H bending bands), 1285, 1250 (C-N stretching bands), 1230 (C=S stretching band), 1158 (ar. C-F stretch band), 836 (aromatic 1,4-disubstitution), 748, 695 (aromatic monosubstitution) peaks. 46. A compound according to Claim 42, wherein, the 1HNMRspectrum of 4-Benzyl- 5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazol-3-thion compound (Formula 2b) comprises 1HNMR (500 MHz) (DMSO- d6 -CH3), 3,44 (common s, EtOH-CH2), 4,43-5,34 (m, 4H, C6H5CH2- and imid.tiy. C3-CH2), 6,10 (s, EtOH-OH), 6,41-7,40 (m, 8H, C6H5CH2-, imid.tiy. C2-H and 4-FPh C3,5-H), 7,42-8,03 (m, 3H, imid.tiy. C5-H and 4-FPh C2,6-H), 13,82 (common s, 1H, NH) peaks. 47. A compound according to Claim 42, wherein, the 13C-NMRspectrum of 4-Benzyl- 5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazol-3-thion compound (Formula 2b) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 19,03 (EtOH CH3), 25,15 (imid.tiy. C3-CH2), 45,87 (CH2C6H5), 56,32 (EtOH CH2), 109,71 (imid.tiy. C5), 111,62 (imid.tiy. C2), 115,31 ; 115,40 (4-FPh C3,5), 126,54 (imid.tiy. C3), 127,18 (4-FPhC2,6), 127,54 (benzylic PhC4), 128,42 (benzylic PhC2,6), 129,21 (benzylic PhC3,5), 130,83 (4-FPh C1), 135,96 (benzylic PhC1), 145,58 (imid.tiy. C6), 148,21 (imid.tiy. C7a), 150,98 (triazole C=N), 160,31 ; 161,33 (4-FPh C4), 167,00 (C=S) peaks. 48. A compound according to Claims 34 or 35, wherein, in the case that R is selected as Formula c, 4-Phenethyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol- 3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-thion compound (Formula 2c) is obtained. 49. A compound according to Claim 48, wherein, the melting temperature of 4- Phenethyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion compound (Formula 2c) is 241-242oC.

50. A compound according to Claim 48, wherein, the 4-Phenethyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3- thion compound (Formula 2c) comprises 60,45; H, 4,53; N, 15,86, by mass (%). 51. A compound according to Claim 48, wherein IR spectrum of 4-Phenethyl-5-((6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol- 3- ): 3106 (N-H stretching band), 3056, 3028, (aromatic C-H stretching bands), 2954, 2858 (aliphatic asymmetric and symmetric C-H stretching bands), 1588, 1574, 1538, 1454 (aromatic C=N and C=C stretching bands), 1415, 1368 (aliphatic asymmetric and symmetric C-H bending bands), 1270, 1206 (C-N stretching bands), 1223 (C=S stretching band), 1156 (ar. C-F stretch band), 840 (aromatic 1,4-disubstitution), 750, 704 (aromatic monosubstitution) peaks. 52. A compound according to Claim 48, wherein, the 1HNMR spectrum of 4-Benzyl- 5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazol-3-thion compound (Formula 2c) comprises 1HNMR (500 MHz) (DMSO- d6 3,00 (t, J = 7,9 Hz, 2H, C6H5CH2CH2), 4,10 (s, 2H, imid.tiy. C3- CH2), 4,22 (t, J = 7,7 Hz, 2H, C6H5CH2CH2), 7,07 (s, 1H, imid.tiy. C2-H), 7,20 7,31 (m, 5H, C6H5-), 7,35 (t, J = 7,1 Hz, 2H, 4-FPh C3,5-H), 7,84 ; 7,86 (dd, J = 8,7 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,01 (s, 1H, imid.tiy. C5-H), 13,65 (common s, 1H, NH) peaks. 53. A compound according to Claim 48, wherein 13C-NMR spectrum of 4-Benzyl-5- ((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazol-3-thion compound (Formula 2c) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 tiy. C3-CH2), 33,67 (triazole, NCH2CH2Ph), 45,34 (triazole, NCH2CH2Ph), 108,72 (imid.tiy. C5), 111,26 (imid.tiy. C2), 115,90 ; 116,07 (4-FPh C3,5), 125,84 (imid.tiy. C3), 127,00 ; 127,07 (4-FPh C2,6), 127,21 (phenethyl Ph C4), 129,11 (phenethyl Ph C2,6), 129,46 (phenethyl Ph C3,5), 131,17 (4-FPh C1), 138,45 (phenethyl Ph C1), 145,60 (imid.tiy. C6), 147,84 (imid.tiy. C7a), 149,20 (triazole C=N), 160,89 ; 162,82 (4-FPh C4), 167,28 (C=S) peaks. 54. A compound according to Claims 34 or 35, wherein, in the case that R is selected as Formula d, 4-(4-Nitrophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2d) is obtained.

55. A compound according to Claim 54, wherein, the melting temperature of 4-(4- Nitrophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2d) is 248-249oC. 56. A compound according to Claim 54, wherein, the 4-(4-Nitrophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3- thion compound (Formula 2d) comprises 53,43; H, 3,62; N, 17,26, by mass (%). 57. A compound according to Claim 54, wherein IR spectrum of 4-(4-Nitrophenyl)-5- ((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazole-3- (N-H stretching band), 3086, 3048 (aromatic C-H stretching bands), 2917, 2849 (aliphatic asymmetric and symmetric C-H stretching bands), 1600, 1372 (NO2 stretching bands), 1583, 1552, 1516, 1468 (aromatic C=N and C=C stretching bands), 1409, 1329 (aliphatic asymmetric and symmetric C-H bending bands), 1258, 1138 (C-N stretching bands), 1221 (C=S stretching band), 1157 (ar. C-F stretch band), 835 (aromatic 1,4-disubstitution), 813 (aromatic 1,4-disubstitution) peaks. 58. A compound according to Claim 54, wherein, the 1HNMR spectrum of 4-(4- Nitrophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2d) comprises 1HNMR (500 MHz) (DMSO-d6 1,22 (common s, EtOH-CH3), 3,42 (common s, EtOH-CH2), 4,24 (s, 2H, imid.tiy. C3-CH2), 5,51 (s, EtOH-OH), 7,33 (t, J = 8,8 Hz, 2H, 4-FPh C3,5-H), 7,47 (s, 1H, imid.tiy. C2-H), 7,78 ; 7,80 (dd, J = 8,8, 3,4 Hz, 2H, 4-FPh C2,6-H), 7,83-7,97 (m, 2H, 4-NO2Ph C2,6-H), 8,00 (s, 1H, imid.tiy. C5-H), 8,05-8,87 (m, 2H, 4-NO2Ph C3,5-H), 13,26 (s, 1H, NH) peaks. 59. A compound according to Claim 54, wherein 13C-NMR spectrum of 4-(4- Nitrophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2d) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 -CH3), 24,62 (imid.tiy. C3-CH2), 56,47 (EtOH-CH2), 108,68 (imid.tiy. C5), 111,82 (imid.tiy. C2), 116,11 ; 116,24 (4-FPh C3,5), 123,03 (4-NO2Ph C2,6), 124,99 (4-NO2Ph C3,5), 125,62 (imid.tiy. C3), 127,24 (4-FPh C2,6), 131,04 ; 131,12 (4-FPh C1), 141,04 (4-NO2Ph C1), 143,14 (imid.tiy. C6), 147,18 (imid.tiy. C7a), 149,26 (triazole C=N), 152,103 (4-NO2Ph C4), 160,21 ; 162,36 (4-FPh C4), 168,54 (C=S) peaks.

60. A compound according to Claims 34 or 35, wherein, in the case that R is selected as Formula e, 4-(2,4-Dichlorophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3- thion compound (Formula 2e) is obtained. 61. A compound according to Claim 60, wherein, the melting temperature of 4-(2,4- Dichlorophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2e) is 234-235oC. 62. A compound according to Claim 60, wherein, the 4-(2,4-Dichlorophenyl)-5-((6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4- triazole-3-thion compound (Formula 2e) comprises 50,18; H, 2,52; N, 14,79, by mass (%). 63. A compound according to Claim 60, wherein, the IR spectrum of 4-(2,4- Dichlorophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3- (KBr, cm ): 3115 (N-H stretching band), 3080, 3061 (aromatic C-H stretching bands), 2906, 2836 (aliphatic asymmetric and symmetric C-H stretching bands), 1585, 1576, 1467, 1412 (aromatic C=N and C=C stretching bands), 1408, 1384 (aliphatic asymmetric and symmetric C-H bending bands), 1264, 1250 (C-N stretching bands), 1214 (C=S stretching band), 1154 (ar. C-F stretch band), 860, 830 (aromatic 1,2,4-trisubstitution), 810 (aromatic 1,4-disubstitution), 737 (ar. C- Cl stretch band) peaks. 64. A compound according to Claim 60, wherein, the 1HNMR spectrum of 4-(2,4- Dichlorophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2e) comprises 1HNMR (500 MHz) (DMSO-d6 4,17 (s, 2H, imid.tiy.C3-CH2), 6,90 (s, 1H imid.tiy. C2-H), 7,23 (t, J =8,8 Hz, 2H, 4-FPh C3,5), 7,64-7,71 (m, 2H, 2,4-diClPh C5,6-H), 7,81 ; 7,84 (dd, J = 8,7, 3,1 Hz, 2H, 4FPh C2,6-H), 7,89 (d, J = 1,3 Hz, 1H, 2,4-diClPh C3-H), 7,99 (s, 1H, imid.tiy. C5-H), 14,05 (s, 1H, NH) peaks. 65. A compound according to Claim 60, wherein 13C-NMR spectrum of 4-(2,4- Dichlorophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3-thion compound (Formula 2e) comprises 13C-NMR (APT) (125 MHz) (DMSO-d6 ): 24,90 (imid.tiy. C3-CH2), 108,38 (imid.tiy. C5), 129,33 (triazole Ph C5), 111,80 (imid.tiy. C2), 115,89 ; 116,06 (4- FPh C3,5), 132,85 (triazole Ph C6), 131,09 (triazole Ph C2), 124,75 (imid.tiy. C3), 127,02; 127,09 (4-FPh C2,6), 130,22 (4-FPh C1), 130,45 (triazole Ph C3), 133,89 (triazole Ph C4), 136,37 (triazole Ph C1), 145,60 (imid.tiy. C6), 147,62 (imid.tiy. C7a), 149,11 (triazole C=N), 160,89 ; 162,83(Ph C4), 168,84 (C=S) peaks. 66. Synthesis method of 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]- N-allyl/aralkyl/arylhydrazinecarbotioamide compounds shown by Formula 1a-e, comprising the process step of: i. adding ethyl 2-aminothiazole-4-acetate dissolved in 10 ml of acetone onto the solution of p-fluorophenacylbromide in 10 ml of acetone, with a mole ratio of 1:1 (p-fluorophenacylbromide:ethyl 2-aminothiazole-4-acetate) and after keeping the resulting mixture at room temperature for a few days, filtering and drying the resulting 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide (Reaction i), ii. boiling 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide in absolute ethanol in a water bath under reflux and drying the precipitated substance by filtration as a result of the reaction and obtaining ethyl 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetate hydrobromide (Reaction ii), iii. adding solid proportion of hydrazine hydrate (98%) on the suspension or solution of ethyl 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide in 60-70 ml of absolute ethanol with mole ratios of 1:5 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide:hydrazine hydrate) and heating in a water bath under reflux for 2-6 hours and then allowing the reaction mixture to cool at room temperature, and filtering the resulting precipitate, purifying it by washing with the appropriate solvent and crystallisation after filtration, and obtaining 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetohydrazide (Reaction iii), iv. heating 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide with appropriate isothiocyanates in absolute ethanol with mole ratios of 1:1 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide:isothiocyanate) under reflux for 1-3 hours and allowing the resulting reaction mixture to cool at room temperature and filtering the resulting precipitate, and then, purifying the obtained substance by washing with 96% ethanol or crystallization and obtaining 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N- allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e) (Reaction iv). . 67. Synthesis method of 4-Allyl/aralkyl/aryl-5-[(6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thion compounds shown by Formula 2a-e, comprising the process steps of; i. adding ethyl 2-aminothiazole-4-acetate dissolved in 10 ml of acetone onto the solution of p-fluorophenacylbromide in 10 ml of acetone, with a mole ratio of 1:1 (p-fluorophenacylbromide:ethyl 2-aminothiazole-4-acetate) and after keeping the resulting mixture at room temperature for a few days, filtering and drying the resulting 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide (Reaction i), ii. boiling 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide in absolute ethanol in a water bath under reflux and drying the precipitated substance by filtration as a result of the reaction and obtaining ethyl 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetate hydrobromide (Reaction ii), iii. adding solid proportion of hydrazine hydrate (98%) on the suspension or solution of ethyl 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide in 60-70 ml of absolute ethanol with mole ratios of 1:5 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide:hydrazine hydrate) and heating in a water bath under reflux for 2-6 hours and then allowing the reaction mixture to cool at room temperature, and filtering the resulting precipitate, purifying it by washing with the appropriate solvent and crystallisation after filtration, and obtaining 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetohydrazide (Reaction iii), iv. heating 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide with appropriate isothiocyanates in absolute ethanol with mole ratios of 1:1 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide:isothiocyanate) under reflux for 1-3 hours and allowing the resulting reaction mixture to cool at room temperature and filtering the resulting precipitate, and then, purifying the obtained substance by washing with 96% ethanol or crystallization and obtaining 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N- allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e) (Reaction iv). v. Heating the 0.005-0.01 mol 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3- yl)acetyl]-N-allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e) in 2N 20 ml NaOH aqueous solution under reflux for 2 hours and allowing the reaction content to cool at room temperature and then acidifying the environment with 12.5% HCl solution and then filtering the resulting precipitate, purification by washing with distilled water, washing with boiling ethanol and crystallisation and thereby obtaining 4-Allyl/aralkyl/aryl-5-[(6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4- triazole-3-thion compounds (Formula 2a-e) (Reaction v). . 68. A compound according to any one of claims 1-65 for use in the inhibition of alpha -glucosidase) enzyme.

69. A pharmaceutical composition comprising a molecule according to any one of claims 1-65. 70. A pharmaceutical composition comprising a compound according to any one of claims 1-65.
Description:
DESCRIPTION HYDRAZINECARBOTHIOAMIDE AND 1,2,4-TRIAZOLE-3-THION DERIVATIVE COMPOUNDS CARRYING IMIDAZO[2,1-b]THIAZOLE RING AND SYNTHESIS METHODS OF THESE COMPOUNDS Technical Field of the Invention The invention relates to hydrazinecarbotioamide and 1,2,4-triazole-3-thion derivative compounds carrying an imidazo[2,1-b]thiazole ring, which have an inhibition activity on -glucosidase) enzyme, and the synthesis methods of these compounds. State of the Art Diabetes is a metabolic disease that occurs as a result of disorders in insulin production its effect, manifests itself with chronic hyperglycemia and progresses with high mortality and morbidity. In diabetes, polyol pathway, glucose oxidation, protein kinase c (PKC) activation, non-enzymatic glycation and formation of advanced glycation products (AGEs) occur. Said hyperglycemia means high blood sugar. Hyperglycemia is the name given to blood glucose levels above 100 mg/dl after fasting for at least 8 hours or blood glucose levels above 140 mg/dl two hours after drinking a sugary drink. Following the chronic hyperglycemia that occurs with diabetes, complications occur in many areas such as the eyes, kidneys, nerves, heart and blood vessels. These complications bring about serious health problems that reduce the quality of life of individuals. With hyperglycemia, the activity of some metabolic pathways increases and diabetes-related complications (vascular complications such as nephropathy, neuropathy and retinopathy) occur with the interactions of the relevant metabolic pathways. There are two types of vascular complications due to the diabetic stress. These are atherosclerosis and diabetic microangiopathy located in large and medium- sized arteries. Atherosclerosis, expressed as arteriosclerosis, can be explained as the stenosis caused by plaques formed in the inner layers of the arteries as a result of the combination of fat, cholesterol and inflammatory wastes. As a result of this stenosis, the blood flow rate slows down and malnutrition of the organs occurs. Diabetic microangiopathy is a complication that disrupts microcirculatory functions at the capillary level. If hyperglycemia results in microangiopathy, a condition called microangiopathy occurs in organs consisting of very thin capillaries such as the kidney and eye. Progressing diabetes results in chronic kidney failure and requires dialysis. If microangiopathy in the eye as a result of hyperglycemia is not treated, a condition that can lead to blindness can be observed. For this reason, diabetic patients require regular nephrology and eye examinations.

In the state of the art, one approach used in the treatment of hyperglycemia is the inhibition of enzymes that hydrolyse starch. In humans, dietary starch is digested by the alpha amylase enzyme in the small intestine and converted into oligosaccharides and disaccharides. Alpha glucosidase enzyme, located on the brush-like surface of the small intestine, is responsible for hydrolysing oligos and disaccharides into monosaccharides. The resulting monosaccharides are absorbed in the intestines. Alpha glucosidase enzyme inhibitors show their effects by competitively inhibiting these enzymes and have an antihyperglycemic effect by indirectly slowing down the rate of glucose absorption. Gastrointestinal hormone levels may also change with these activities of alpha glucosidase enzyme inhibitors. Although acarbose, which is used today in the inhibition of alpha glucosidase enzyme, seems to be effective in this inhibition, this effect is not at the desired levels.

Although acarbose is used in the state of the art as an alpha enzyme inhibitor in the treatment of diabetes, which is a metabolic disease that manifests itself especially with chronic hyperglycemia and progresses with high mortality and morbidity, the effect provided by the alpha glucosidase inhibition provided by the alpha glucosidase inhibitor group drug in question is insufficient. As a result, it became necessary to develop a new compound to provide alpha glucosidase inhibition.

Brief Description and Aims of the Invention

In the invention, hydrazinecarbotioamide and 1 ,2,4-triazole-3-thion derivative compounds carrying an imidazo[2,1-b]thiazole ring, which have an inhibition activity on the alpha glucosidase (a-glucosidase) enzyme, and the synthesis methods of these compounds are described. The general structure of the molecules of the invention is shown by Formula X. Formula X One aim of the invention is to produce compounds that have a higher inhibitory effect -glucosidase) enzyme than drugs such as acarbose, etc., which are used as alpha glucosidase enzyme inhibitors in the state of the art. The preparation of said compounds is achieved by the synthesis method of hydrazinecarbotioamide and 1,2,4-triazole-3-thion derivative compounds carrying imidazo[2,1-b]thiazole ring. Description of Drawings Figure 1. IR spectrum of the compound 2-[2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl]-N-allylhydrazine-1-carbotioamide Figure 2. 1 H-NMR spectrum of the compound 2-[2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl]-N-allylhydrazine-1-carbotioamide Figure 3. 13 C-NMR (APT) spectrum of the compound 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-allylhydra zine-1-carbotioamide Figure 4. IR spectrum of the compound 2-[2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1-carbotioamide Figure 5. 1 H-NMR spectrum of the compound 2-[2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl]-N-benzylhydrazine-1-carbotioamide Figure 6. 13 C-NMR (APT) spectrum of the compound 2-[2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N-benzylhydr azine-1-carbotioamide Figure 7. IR spectrum of the compound 2-(2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl)-N-phenethylhydrazine-1-carbotioamide Figure 8. 1 H-NMR spectrum of the compound 2-(2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl)-N-phenethylhydrazine-1-carbotioamide Figure 9. 13 C-NMR (APT) spectrum of the compound 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-phenethylh ydrazine-1- carbotioamide Figure 10. IR spectrum of the compound 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitroph enyl)hydrazine-1- carbotioamide Figure 11. 1 H-NMR spectrum of the compound 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitroph enyl)hydrazine-1- carbotioamide Figure 12. 13 C-NMR (APT) of the compound 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(4-nitroph enyl)hydrazine-1- carbotioamide Figure 13. IR spectrum of the compound 2-(2-(6-(4-Fluorophenyl)imidazo[2,1- b]thiazol-3-yl)acetyl)-N-(2,4-dichlorophenyl)hydrazine-1-car botioamide Figure 14. 1 H-NMR spectrum of the compound 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4-dichl orophenyl)hydrazine-1- carbotioamide Figure 15. 13 C-NMR (APT) spectrum of the compound 2-(2-(6-(4- Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N-(2,4-dichl orophenyl)hydrazine-1- carbotioamide Figure 16. IR spectrum of the compound 4-Allyl-5-((6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-thion Figure 17. 1 H-NMR spectrum of the compound 4-Allyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 18. 13 C-NMR (APT) spectrum of the compound 4-Allyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 19. IR spectrum of the compound4-Benzyl-5-((6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-thion Figure 20. 1 H-NMR spectrum of the compound 4-Benzyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 21. 13 C-NMR (APT) spectrum of the compound 4-Benzyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 22. IR spectrum of the compound 4-Phenethyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 23. 1 H-NMR spectrum of the compound 4-Phenethyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 24. 13 C-NMR (APT) spectrum of the compound 4-Phenethyl-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion Figure 25. IR spectrum of the compound 4-(4-Nitrophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thion Figure 26. 1 H-NMR spectrum of the compound 4-(4-Nitrophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thion Figure 27. 13 C-NMR (APT) spectrum of the compound 4-(4-Nitrophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thion Figure 28. IR spectrum of the compound 4-(2,4-Dichlorophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thion Figure 29. 1 H-NMR spectrum of the compound 4-(2,4-Dichlorophenyl)-5-((6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thion Figure 30. 13 C-NMR (APT) spectrum of the compound 4-(2,4-Dichlorophenyl)-5-((6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-2,4-dihyd ro-3H-1,2,4-triazole-3- thion Detailed Description of the Invention The invention relates to hydrazinecarbotioamide and 1,2,4-triazole-3-thion derivative compounds carrying an imidazo[2,1-b]thiazole ring, which have an inhibition activity on -glucosidase) enzyme, and the synthesis methods of these compounds. The compounds of the invention have a higher inhibition activity than acarbose, which is known in the state of the art and has an inhibition activity on the alpha glucosidase enzyme. The general structure of the molecules of the invention is shown by Formula X. Formula X wherein R is selected from the formulas below:

The compound obtained in the case that the R group is R= in said Formula is shown by formula 1a-e. The compound obtained in the case that the R group is R= in said Formula is shown by formula 2a-e. In Formula 1a-e and Formula 2a-e, R is selected from the following formulas; R =-CHCH=CH, , 2 2 Formula Formula c , The 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N -allylhydrazine-1- carbotioamide compound obtained in the case that R group in Formula 1a-e is R = - CH2CH=CH2 is shown by Formula 1a. It was synthesized with a yield of 64-95% and its melting temperature is in the range of 228-229 o C. Elemental analysis findings (C17H16FN5OS2): by mass (%), C, 52.37; H, 4.25; N, 17.91. 1 ): 3221, 3138 (N-H stretching bands), 3061 (aromatic C-H stretching band), 2978, 2885 (aliphatic asymmetric and symmetric C-H stretching bands), 1674 (amide I, C=O stretching band), 1606, 1548, 1492, 1463 (amide II and aromatic C=N and C=C stretching bands), 1406, 1381 (aliphatic asymmetric and symmetric C-H bending bands), 1301, 1240 (amide III N-H bending and C-N stretching bands), 1215 (C=S stretch band), 1157 (ar. C-F stretch band), 852 (aromatic 1,4- disubstitution). 1 H NMR (500 MHz) (DMSO-d 6 (ppm): 3,85 (s, 2H, CH 2 CONH), 4,16 (s, 2H, N-CH2-CH=CH2), 5,04, 5,06 (dd, J = 10,3 ; 1,8 Hz, 1H, CH=CH2, cis), 5,14, 5,17 (dd, J = 17,2 ; 1,8 Hz, 1H, CH = CH 2 , trans), 5,80-5,92 (m, 1H, CH=CH 2 ), 7,10 (s, 1H, imid.tiy. C2-H), 7,25 (t, J = 8.9 Hz, 2H, 4-FPh C3,5-H), 7,84 ; 7,86 (dd, J = 8,8 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,15 (s, 1H, imid.tiy. C5-H), 8,34 (s, 1H, NH), 9,40 (s, 1H, NH), 10,21 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 33,14 (CH2CONH), 46,36 (CH2- CH=CH2), 108,88 (imid.tiy. C5), 110,90 (imid.tiy. C2), 115,72 (CH=CH2), 115,88 ; 116,05 (4-FPh C3,5), 126,60 (imid.tiy. C3), 126,92 ; 126,98 (4-FPh C2,6), 131,28 ; 131,30 (4-FPh C1), 135,29 (CH=CH2), 145,49 (imid.tiy. C6), 149,10 (imid.tiy. C7a), 160,85 ; 162,79 (Ph C4), 167,20 (CONH), 171,57 (C=S). The 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N -allylhydrazine-1- carbotioamide compound obtained in the case that R group in Formula 1a-e is R = is shown by Formula 1b.

Formula 1b It was synthesized with a yield of 64-95% and its melting temperature is 245-246 o C. Elemental analysis findings (C21H18FN5OS2): by mass (%), C, 57.08; H, 4.22; N, 16.02. 1): 3240, 3149 (N-H stretch band), 3064 (aromatic C-H stretch band), 2972, 2883 (aliphatic asymmetric and symmetric C-H stretch bands), 1672 (amide I C=O stretching band), 1587, 1548, 1489, 1463 (amide II and aromatic C=N and C=C stretching bands), 1409, 1381 (aliphatic asymmetric and symmetric C-H bending bands), 1300, 1261 (amide III N-H bending and C-N stretching bands), 1215 (C=S stretch band), 1151 (ar. C-F stretch band), 848 (aromatic 1,4-disubstitution), 731, 692 (aromatic monosubstitution). ). 1 H NMR (500 MHz) (DMSO-d6 3,84 (s, 2H, CH2CONH), 4,78 (d, J = 5,9 Hz, 2H, NH-CH2-C6H5), 7,09 (s, 1H, imid.tiy. C2-H), 7,17-7,41 (m, 7H, 4-FPh C3,5- H and benzyl), 7,79, 7,81 (dd, J = 8,8 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,13 (s, 1H, imid.tiy. C5-H), 8,70 (s, 1H, NH), 9,47 (s, 1H, NH), 10,26 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 2CONH), 47,19 (NHCH2), 108,86 (imid.tiy. C5), 110,89 (imid.tiy. C2), 115,87 ; 116,04 (4-FPh C3,5), 126,59 (imid.tiy. C3), 126,92 ; 126,99 (4-FPh C2,6), 127,12 (benzylic Ph C4), 127,38 (benzylic Ph C2,6), 128,55 (benzylic Ph C3,5), 131,26 ; 131,29 (4-F Ph C1), 139,64 (benzylic Ph C1), 145,43 ; 145,51 (imid. tiy. C6), 149,10 (imid. tiy. C7a), 160,83 ; 162,77 (4-FPh C4), 167,29 (CONH), 171,50 (C=S). The 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N -phenethylhydrazine- 1-carbotioamide compound obtained in the case that R group in Formula 1a-e is R = Formula 1c It was synthesized with a yield of 64-95% and its melting temperature is 220-221 o C. Elemental analysis C22H20FN5OS2: by mass (%), C, 58.26; H, 4.59; N, 15.50. 1): 3248, 3142 (N-H stretching bands), 3076 (aromatic C-H stretching band), 2962, 2875 (aliphatic asymmetric and symmetric C-H stretching bands), 1672 (amide I, C=O stretching band), 1600, 1546, 1490, 1463 (amide II and aromatic C=N and C=C stretching bands), 1415, 1350 (aliphatic asymmetric and symmetric C-H bending bands), 1292, 1285 (amide III N-H bending and C-N stretching band), 1213 (C=S stretching band), 1149 (ar. C-F stretch band), 846 (aromatic 1,4- disubstitution), 731, 694 (aromatic monosubstitution). 1 H NMR (500 MHz) (DMSO-d6 2,85 (t, J = 8,0 Hz, 2H, NHCH2CH2Ph), 3,64-3,79 (m, 2H, NHCH2CH2Ph), 3,86 (s, 2H, CH2CONH), 7,11 (s, 1H, imid.tiy. C2-H), 7,17-7,29 (m.5H, -CH2CH2C6H5), 7,31 (t, J = 7,5 Hz, 2H, 4-FPh C3,5-H), 7,86, 7,88 (dd, J = 8,6 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,21 (s, 1H, imid.tiy. C5-H), 8,28 (s, 1H, NH), 9,40 (s, 1H, NH), 10,23 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO- 33,15 (CH2CONH), 35,43 (NHCH2CH2Ph), 45,80 (NHCH2CH2Ph), 108,86 (imid.tiy. C5), 110,94 (imid.tiy. C2), 115,89 ; 116,06 (4-FPh C3,5), 126,58 (imid.tiy. C3), 126,65 (phenethyl Ph C4), 126,93, 126,99 (4-FPh C2,6), 128,79, 128,89 (phenethyl Ph C2,6), 129,06; 129,12 (phenethyl Ph C3,5), 131,30; 131,32 (4-FPh C1), 139,61 (phenethyl Ph C1), 145,43; 145,55 (imid.tiy. C6), 149,14 (imid.tiy. C7a), 160,85 ; 162,79 (4-FPh C4), 167,18 (CONH), 171,67 (C=S). 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N -(4- nitrophenyl)hydrazine-1-carbotioamide compound obtained in the case that R group in Formula 1a-e is R = is shown by Formula 1d. Formula 1d It was synthesized with a yield of 64-95% and its melting temperature is 214-215 o C. Elemental analysis findings C20H15FN6O3S2.0,5H2O: by mass (%), C, 50.26; H, 3.31; N, 17.92. 1): 3286, 3119 (N-H stretching bands), 3095 (aromatic C-H stretching band), 2902, 2846 (aliphatic asymmetric and symmetric C-H stretching bands), 1681 (amide I C=O stretching band), 1596, 1325 (NO2 stretching bands), 1603, 1533, 1509, 1441 (amide II and aromatic C=N and C=C stretching bands), 1415, 1369 (aliphatic asymmetric and symmetric C-H bending bands), 1299, 1262 (amide III N-H bending and C-N stretching bands), 1217 (C=S stretching band), 1154 (ar. C-F stretch band), 835, 817 (aromatic 1,4-disubstitution). 1 H NMR (500 MHz) (DMSO-d6 3,94 (s, 2H, CH2CONH), 7,15 (s, 1H, imid.tiy. C2-H), 7,24 (t, J = 8,7 Hz, 2H, 4-FPh C3,5-H), 7,73-7,87 (m, 2H, 4-FPh C2,6-H), 7,93 (d, J = 7,7 Hz, 2H, 4-NO2Ph C2,6-H), 8,05-8,41 (m, 3H, imid.tiy. C5-H and 4-NO2Ph C3,5-H), 10,15 (s, 1H, NH), 10,51 (s, 1H, NH), 10,89 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 33,22 (CH2CONH), 108,83 (imid.tiy. C 5 ), 111,23 (imid.tiy. C 2 ), 115,91 ; 116,08 (4-FPh C 3,5 ), 117,01 (4-NO 2 Ph C 2,6 ), 125,99 (4-NO2Ph C3,5), 126,48 (imid.tiy. C3), 126,91 ; 126,98 (4-FPh C2,6), 131,09 ; 131,11 (4-FPh C 1 ), 145,38 (imid.tiy. C 6 ), 147,06 (4-NO 2 Ph C 1 ), 149,12 (imid.tiy. C 7a ), 156,45 (4-NO2Ph C4), 160,88 ; 162,82 (4-FPh C4), 166,94 (CONH), 171,52 (C=S). The 2-(2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl)-N -(2,4- dichlorophenyl)hydrazine-1- group in Formula 1a- is shown by Formula 1e. Formula 1e It was synthesized with a yield of 64-95% and its melting temperature is in the range of 207-208 o C. Elemental analysis findings (C20H14Cl2FN5OS2.0,5H2O): by mass (%), C, 47.42; H, 2.93; N, 13.90. 1): 3208 (N-H stretching band), 3098, 3057 (aromatic C-H stretching bands), 2965, 2895 (aliphatic asymmetric and symmetric C-H stretching bands), 1678 (amide I, C=O stretching band), 1597, 1546, 1494, 1463 (amide II and aromatic C=N and C=C stretching bands), 1406, 1384 (aliphatic asymmetric and symmetric C-H bending bands), 1285, 1260 (amide III N-H bending and C-N stretching bands), 1224 (C=S stretching band), 1154 (ar. C-F stretch band), 866, 808 (aromatic 1,2,4-trisubstitution), 848 (aromatic 1,4-disubstitution), 739 (ar. C-Cl stretch band). 1 H NMR (500 MHz) (DMSO-d 6 3,90 (s, 2H, CH 2 CONH), 7,16 (s, 1H, imid.tiy. C2-H), 7,24 (t, J = 8,8 Hz, 2H, 4-FPh C3,5-H), 7,34-7,42 (m, 1H, 2,4-diClPh C3- H), 7,43, 7,45 (dd, J = 8,5 ; 2,4 Hz, 1H, 2,4-diClPh C 5 -H), 7,68-7,73 (m, 1H, 2,4-diClPh C6-H), 7,80, 7,81 (dd, J = 8,7 ; 3,0 Hz, 2H, 4FPh C2,6-H), 8,19 (s, 1H, imid.tiy. C5-H), 9,70 (s, 1H, NH), 9,94 (s, 1H, NH), 10,49 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 33,05 (CH2CONH), 109,10 (imid.tiy. C5), 111,48 (imid.tiy. C2), 115,97 ; 116,15 (4-FPh C3,5), 126,72 (imid.tiy. C3), 127,00 ; 127,07 (4-FPh C2,6), 127,91 (2,4-diClPh C6), 129,39 (2,4-diClPh C5), 132,91 (2,4 diClPh C3), 130,67 (2,4-diClPh C2), 132,25 (4-FPh C1), 133,29 (2,4-diClPh C4), 136,42 (2,4-diClPh C1), 144,79 (imid.tiy. C6), 148,99 (imid.tiy. C7a), 160,96 ; 162,89 (4- FPh C4), 167,27 (CONH), 171,60 (C=S). The 4-Allyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)met hyl)-2,4-dihydro-3H- 1,2,4-triazol-3- -e is -CH2CH=CH2 is shown by Formula 2a. Formula 2a It was synthesized with a yield of 64-95% and its melting temperature is in the range of 277-278 o C. Elemental analysis findings (C17H14FN5 S 2): by mass (%), C, 54.66; H, 3.89; N, 18.42. 1): 3412, 3108 (N-H stretching bands), 3078, 3016 (aromatic C-H stretching bands), 2980, 2891 (aliphatic asymmetric and symmetric C-H stretching bands), 1596, 1548, 1532, 1452 (aromatic C=N and C=C stretching bands), 1412, 1345 (aliphatic asymmetric and symmetric C-H bending bands), 1287, 1237 (C-N stretching bands), 1221 (C=S stretching band), 1147 (ar. C-F stretch band), 835 (aromatic 1,4-disubstitution). 1 H NMR (500 MHz) (DMSO-d 6 4,44 (s, 2H, imid.tiy. C 3 -CH 2 ), 4,77 (d, J = 6,2 Hz, 2H, N-CH2-CH=CH2), 5,07, 5,11 (dd, J = 17,2, 1,5 Hz, 1H CH = CH2, trans), 5,18, 5,20 (dd, J = 10,4, 1,5 Hz, 1H, CH=CH2, cis), 5,85 5,95 (m, 1H, CH=CH2), 7,29 (t, J = 8,8 Hz, 2H, 4-FPh C3,5-H), 7,35 (s, 1H, imid.tiy. C2-H), 7,87 ; 7,89 (dd, J = 8,7 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,33 (s, 1H, imid.tiy. C5-H), 13,77 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 24,48 (imid.tiy. C3-CH2), 45,63 (triazole NCH2CH=CH2), 109,50 (imid.tiy. C5), 113,40 (imid.tiy. C2), 116,18 ; 116,36 (4- FPh C3,5), 118,20 (triazole NCH2CH=CH2), 126,16 (imid.tiy. C3), 127,35; 127,41 (4- FPh C2,6), 129,02 (4-FPh C1), 131,72 (triazole NCH2CH=CH2), 142,96 (imid.tiy. C6), 148,11 (imid.tiy. C7a), 148,72 (triazole C=N), 161,25 ; 163,20 (4-FPh C4), 167,66 (C=S). The 4-Benzyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl)me thyl)-2,4-dihydro-3H- 1,2,4-triazol-3- -e is R = is shown by Formula 2b.

Formula 2b It was synthesized with a yield of 64-95% and its melting temperature is in the range of 273-274 o C. Elemental analysis findings (C21H16FN5S2.EtOH): by mass (%), C, 58.76; H, 4.85; N, 14.67. 1): 3134 (N-H stretching band), 3098, 3020 (aromatic C-H stretching bands), 2916, 2878 (aliphatic asymmetric and symmetric C-H stretching bands), 1594, 1564, 1512, 1450 (aromatic C=N and C=C stretching bands), 1419, 1374 (aliphatic asymmetric and symmetric C-H bending bands), 1285, 1250 (C-N stretching bands), 1230 (C=S stretching band), 1158 (ar. C-F stretch band), 836 (aromatic 1,4-disubstitution), 748, 695 (aromatic monosubstitution). 1 HNMR (500 MHz) (DMSO-d6 1,05 (common s, EtOH-CH3), 3,44 (common s, EtOH-CH2), 4,43-5,34 (m, 4H, C6H5CH2- and imid.tiy. C3-CH2), 6,10 (s, EtOH-OH), 6,41-7,40 (m, 8H, C6H5CH2-, imid.tiy. C2-H and 4-FPh C3,5-H), 7,42-8,03 (m, 3H, imid.tiy. C 5 -H and 4-FPh C 2,6 -H), 13,82 (common s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d 6 19,03 (EtOH CH 3 ), 25,15 (imid.tiy. C3-CH2), 45,87 (CH2C6H5), 56,32 (EtOH CH2), 109,71 (imid.tiy. C5), 111,62 (imid.tiy. C 2 ), 115,31 ; 115,40 (4-FPh C 3,5 ), 126,54 (imid.tiy. C 3 ), 127,18 (4-FPhC 2,6 ), 127,54 (benzylic PhC4), 128,42 (benzylic PhC2,6), 129,21 (benzylic PhC3,5), 130,83 (4- FPh C1), 135,96 (benzylic PhC1), 145,58 (imid.tiy. C6), 148,21 (imid.tiy. C7a), 150,98 (triazole C=N), 160,31 ; 161,33 (4-FPh C4), 167,00 (C=S). The 4-Phenethyl-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl )methyl)-2,4-dihydro- 3H-1,2,4-triazol-3-thion compound obtained in the case that R group in Formula 2a-e is R = . Formula 2c It was synthesized with a yield of 64-95% and its melting temperature is in the range of 241-242 o C. Elemental analysis findings (C 22 H 18 FN 5 S 2 ): by mass (%), C, 60.45; H, 4.53; N, 15.86. 1): 3106 (N-H stretching band), 3056, 3028, (aromatic C-H stretching bands), 2954, 2858 (aliphatic asymmetric and symmetric C-H stretching bands), 1588, 1574, 1538, 1454 (aromatic C=N and C=C stretching bands), 1415, 1368 (aliphatic asymmetric and symmetric C-H bending bands), 1270, 1206 (C-N stretching bands), 1223 (C=S stretching band), 1156 (ar. C-F stretch band), 840 (aromatic 1,4-disubstitution), 750, 704 (aromatic monosubstitution). 1 HNMR (500 MHz) (DMSO-d6 3,00 (t, J = 7,9 Hz, 2H, C6H5CH2CH2), 4,10 (s, 2H, imid.tiy. C3-CH2), 4,22 (t, J = 7,7 Hz, 2H, C6H5CH2CH2), 7,07 (s, 1H, imid.tiy. C2-H), 7,20 7,31 (m, 5H, C6H5-), 7,35 (t, J = 7,1 Hz, 2H, 4-FPh C3,5-H), 7,84 ; 7,86 (dd, J = 8,7 ; 3,2 Hz, 2H, 4-FPh C2,6-H), 8,01 (s, 1H, imid.tiy. C5-H), 13,65 (common s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 24,45 (imid.tiy. C3-CH2), 33,67 (triazole, NCH2CH2Ph), 45,34 (triazole, NCH2CH2Ph), 108,72 (imid.tiy. C5), 111,26 (imid.tiy. C2), 115,90 ; 116,07 (4-FPh C3,5), 125,84 (imid.tiy. C3), 127,00 ; 127,07 (4- FPh C2,6), 127,21 (phenethyl Ph C4), 129,11 (phenethyl Ph C2,6), 129,46 (phenethyl Ph C 3,5 ), 131,17 (4-FPh C 1 ), 138,45 (phenethyl Ph C 1 ), 145,60 (imid.tiy. C 6 ), 147,84 (imid.tiy. C7a), 149,20 (triazole C=N), 160,89 ; 162,82 (4-FPh C4), 167,28 (C=S). The 4-(4-Nitrophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]thiazo l-3-yl)methyl)-2,4- dihydro-3H-1,2,4-triazole-3- Formula 2a- is shown by Formula 2d. Formula 2d It was synthesized with a yield of 64-95% and its melting temperature is in the range of 248-249 o C. Elemental analysis findings (C20H13FN6O2S2.0,5EtOH): by mass (%), C, 53.43; H, 3.62; N, 17.26. 1): 3130 (N-H stretching band), 3086, 3048 (aromatic C-H stretching bands), 2917, 2849 (aliphatic asymmetric and symmetric C-H stretching bands), 1600, 1372 (NO2 stretching bands), 1583, 1552, 1516, 1468 (aromatic C=N and C=C stretching bands), 1409, 1329 (aliphatic asymmetric and symmetric C-H bending bands), 1258, 1138 (C-N stretching bands), 1221 (C=S stretching band), 1157 (ar. C-F stretch band), 835 (aromatic 4-trisubstitution), 813 (aromatic 1,4- disubstitution). 1 HNMR (500 MHz) (DMSO-d6 1,22 (common s, EtOH-CH3), 3,42 (common s, EtOH-CH2), 4,24 (s, 2H, imid.tiy. C3-CH2), 5,51 (s, EtOH-OH), 7,33 (t, J = 8,8 Hz, 2H, 4-FPh C3,5-H), 7,47 (s, 1H, imid.tiy. C2-H), 7,78 ; 7,80 (dd, J = 8,8, 3,4 Hz, 2H, 4-FPh C 2,6 -H), 7,83-7,97 (m, 2H, 4-NO 2 Ph C 2,6 -H), 8,00 (s, 1H, imid.tiy. C 5 -H), 8,05-8,87 (m, 2H, 4-NO2Ph C3,5-H), 13,26 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 19,18 (EtOH-CH3), 24,62 (imid.tiy. C 3 -CH 2 ), 56,47 (EtOH-CH 2 ), 108,68 (imid.tiy. C 5 ), 111,82 (imid.tiy. C 2 ), 116,11 ; 116,24 (4-FPh C3,5), 123,03 (4-NO2Ph C2,6), 124,99 (4-NO2Ph C3,5), 125,62 (imid.tiy. C3), 127,24 (4-FPh C2,6), 131,04 ; 131,12 (4-FPh C1), 141,04 (4-NO2Ph C1), 143,14 (imid.tiy. C6), 147,18 (imid.tiy. C7a), 149,26 (triazole C=N), 152,103 (4-NO2Ph C4), 160,21 ; 162,36 (4-FPh C4), 168,54 (C=S). The 4-(2,4-Dichlorophenyl)-5-((6-(4-fluorophenyl)imidazo[2,1-b]t hiazol-3-yl)methyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thion compound obtained in the case that R group in Formula 2a-e is R = is shown by Formula 2e. It was synthesized with a yield of 64-95% and its melting temperature is in the range of 234-235 o C. Elemental analysis findings (C20H12Cl2FN5S2): by mass (%), C, 50.18; H, 2.52; N, 14.79. 1): 3115 (N-H stretching band), 3080, 3061 (aromatic C-H stretching bands), 2906, 2836 (aliphatic asymmetric and symmetric C-H stretching bands), 1585, 1576, 1467, 1412 (aromatic C=N and C=C stretching bands), 1408, 1384 (aliphatic asymmetric and symmetric C-H bending bands), 1264, 1250 (C-N stretching bands), 1214 (C=S stretching band), 1154 (ar. C-F stretch band), 860, 830 (aromatic 1,2,4-trisubstitution), 810 (aromatic 1,4-disubstitution), 737 (ar. C-Cl stretch band). 1HNMR (500 MHz) (DMSO-d6 4,17 (s, 2H, imid.tiy.C3-CH2), 6,90 (s, 1H imid.tiy. C2-H), 7,23 (t, J =8,8 Hz, 2H, 4-FPh C3,5), 7,64-7,71 (m, 2H, 2,4-diClPh C5,6-H), 7,81 ; 7,84 (dd, J = 8,7, 3,1 Hz, 2H, 4FPh C2,6-H), 7,89 (d, J = 1,3 Hz, 1H, 2,4- diClPh C3-H), 7,99 (s, 1H, imid.tiy. C5-H), 14,05 (s, 1H, NH). 13 C-NMR (APT) (125 MHz) (DMSO-d6 24,90 (imid.tiy. C3-CH2), 108,38 (imid.tiy. C5), 129,33 (triazole Ph C5), 111,80 (imid.tiy. C2), 115,89 ; 116,06 (4-FPh C3,5), 132,85 (triazole Ph C6), 131,09 (triazole Ph C2), 124,75 (imid.tiy. C3), 127,02; 127,09 (4-FPh C2,6), 130,22 (4-FPh C1), 130,45 (triazole Ph C3), 133,89 (triazole Ph C4), 136,37 (triazole Ph C1), 145,60 (imid.tiy. C6), 147,62 (imid.tiy. C7a), 149,11 (triazole C=N), 160,89 ; 162,83(Ph C4), 168,84 (C=S). Synthesis steps of hydrazinecarbotioamide and 1,2,4-triazole-3-thion derivative compounds carrying imidazo[2,1-b]thiazole ring, which have an inhibition activity on -glucosidase) enzyme of the invention are shown below as Reaction i, Reaction ii, Reaction iii, Reaction iv, Reaction v, respectively. Synthesis method of 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N - allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e), one of the compounds that are subject of the invention comprises the process step of: i. adding ethyl 2-aminothiazole-4-acetate dissolved in 10 ml of acetone onto the solution of p-fluorophenacylbromide in 10 ml of acetone, with a mole ratio of 1:1 (p-fluorophenacylbromide:ethyl 2-aminothiazole-4-acetate) and after keeping the resulting mixture at room temperature for a few days, filtering and drying the resulting 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide (Reaction i), ii. boiling 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide in absolute ethanol in a water bath under reflux and drying the precipitated substance by filtration as a result of the reaction and obtaining ethyl 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetate hydrobromide (Reaction ii), iii. adding solid proportion of hydrazine hydrate (98%) on the suspension or solution of ethyl 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide in 60-70 ml of absolute ethanol with mole ratios of 1:5 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide:hydrazine hydrate) and heating in a water bath under reflux for 2-6 hours and then allowing the reaction mixture to cool at room temperature, and filtering the resulting precipitate, purifying it by washing with the appropriate solvent and crystallisation after filtration, and obtaining 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetohydrazide (Reaction iii), iv. heating 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazi de with appropriate isothiocyanates in absolute ethanol with mole ratios of 1:1 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide:is othiocyanate) under reflux for 1-3 hours and allowing the resulting reaction mixture to cool at room temperature and filtering the resulting precipitate, and then, purifying the obtained substance by washing with 96% ethanol or crystallization and obtaining 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N - allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e) (Reaction iv). Synthesis method of 4-Allyl/aralkyl/aryl-5-[(6-(4-fluorophenyl)imidazo[2,1-b]thi azol-3- yl)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thion compounds (Formula 2a-e), one of the compounds that are subject of the invention, comprise the process steps of; i. adding ethyl 2-aminothiazole-4-acetate dissolved in 10 ml of acetone onto the solution of p-fluorophenacylbromide in 10 ml of acetone, with a mole ratio of 1:1 (p-fluorophenacylbromide:ethyl 2-aminothiazole-4-acetate) and after keeping the resulting mixture at room temperature for a few days, filtering and drying the resulting 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide (Reaction i), ii. boiling 2-amino-3-[(4-fluorobenzoyl)methyl]-4- (ethoxycarbonylmethyl)thiazolium bromide in absolute ethanol in a water bath under reflux and drying the precipitated substance by filtration as a result of the reaction and obtaining ethyl 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetate hydrobromide (Reaction ii), iii. adding solid proportion of hydrazine hydrate (98%) on the suspension or solution of ethyl 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide in 60-70 ml of absolute ethanol with mole ratios of 1:5 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide:hydrazine hydrate) and heating in a water bath under reflux for 2-6 hours and then allowing the reaction mixture to cool at room temperature, and filtering the resulting precipitate, purifying it by washing with the appropriate solvent and crystallisation after filtration, and obtaining 2-[6-(4-fluorophenyl)imidazo[2,1- b]thiazol-3-yl]acetohydrazide (Reaction iii), iv. heating 2-[6-(4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazi de with appropriate isothiocyanates in absolute ethanol with mole ratios of 1:1 (2-[6- (4-fluorophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide:is othiocyanate) under reflux for 1-3 hours and allowing the resulting reaction mixture to cool at room temperature and filtering the resulting precipitate, and then, purifying the obtained substance by washing with 96% ethanol or crystallization and obtaining 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3-yl)acetyl]-N - allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e) (Reaction iv). v. Heating the 0.005-0.01 mol 2-[2-(6-(4-Fluorophenyl)imidazo[2,1-b]thiazol-3- yl)acetyl]-N-allyl/aralkyl/arylhydrazinecarbotioamide compounds (Formula 1a-e) in 2N 20 ml NaOH aqueous solution under reflux for 2 hours and allowing the reaction content to cool at room temperature and then acidifying the environment with 12.5% HCl solution and then filtering the resulting precipitate, purification by washing with distilled water, washing with boiling ethanol and crystallisation and thereby obtaining 4-Allyl/aralkyl/aryl-5-[(6-(4- fluorophenyl)imidazo[2,1-b]thiazol-3-yl)methyl]-2,4-dihydro- 3H-1,2,4- triazole-3-thion compounds (Formula 2a-e) (Reaction v). Table 1. Inhibition activities of the compounds of the invention on alpha glucosidase -glucosidase) enzyme. As can be clearly seen from Table 1, the concentrations of the compounds 1d, 1e, 2a- 2d, which are the subject of the invention, inhibiting the alpha glucosidase enzyme are lower than acarbose. In other words, said compounds can create inhibition on the alpha glucosidase enzyme by using less amounts of acarbose, which is used as an alpha glucosidase enzyme inhibitor in the state of the art.




 
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