Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors

European Journal of Medicinal Chemistry

Volumn 45, Issue 11, 2010, Pages 4953-4962

  Zhu, Yanyun ^a   Xia, Shuang ^a   Zhu, Mingjie ^b   Yi, Weiyin ^b   Cheng, Jiagao ^a   Song, Gonghua ^a   Li, Zhong ^a   Lu, Peng ^b  

^a EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b Shanghai Sun Sail Pharmaceutical Science and Technology Co Ltd   (China)

Author keywords

Anti diabetic agent; Dipeptidyl peptidase IV inhibitor; Imidazopyrazinone; Molecular docking

Indexed keywords

3 (BENZYLOXYAMINO) 1 [2 BENZYL HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 4 (2,4,5 TRIFLUOROPHENYL)BUTAN 1 ONE; 3 (BENZYLOXYAMINO) 1 [2 ETHYL HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZIN 7(8H) YL] 4 (2,4,5 TRIFLUOROPHENYL)BUTAN 1 ONE; 3 (BENZYLOXYAMINO) 1 [2 METHYL HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 4 (2,4,5-TRIFLUOROPHENYL)BUTAN 1 ONE; 3 (BENZYLOXYAMINO) 1 [HEXAHYDRO 3 OXO OXAZOLO[1,5 A]PYRAZIN 7(8H) YL] 4 (2,4,5 TRIFLUOROPHENYL)BUTAN 1 ONE; 3 (BENZYLOXYAMINO) 1 [HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZIN 7(8H) YL] 4 (2,4,5 TRIFLUOROPHENYL)BUTAN 1 ONE; 4 (2,4,5 TRIFLUOROPHENYL) 3 OXOBUTANOIC ACID; 4 (2,4,5 TRIFLUOROPHENYL) AMINOBUTANOIC ACID; 4 (2,4,5 TRIFLUOROPHENYL) HYDROXYBUTANOIC ACID; ANTIDIABETIC AGENT; DI TERT BUTYL 2 (AMINOMETHYL)PIPERAZINE 1,4 DICARBOXYLATE; DI TERT BUTYL 2 [(1,3 DIOXOISOINDOLIN 2 YL)METHYL] PIPERAZINE 1,4 DICARBOXYLATE; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; HEXAHYDRO 2 (4 TRIFLUOROMETHYLPHENYL) IMIDAZO[1,5 A]PYRAZIN 3 ONE; HEXAHYDRO 2 BENZYL IMIDAZO[1,5 A]PYRAZIN 3 ONE; N BENZYLOXY 4 (2,4,5 TRIFLUOROPHENYL) AMINOBUTANOIC ACID; N BENZYLOXY 4 (2,4,5 TRIFLUOROPHENYL) HYDROXYBUTANAMIDE 3; N BENZYLOXY [1 METHYL (2,4,5 TRIFLUOROBENZYL)] 2 OXOAZETIDINE; SITAGLIPTIN; TERT BUTYL HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZINE 7(1H) CARBOXYLATE; TERT BUTYL[3 [2 (3 CYANOBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (3 METHOXYBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (3,5 DIMETHOXYBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (4 CHLOROBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (4 CYANOPHENYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (4 FLUOROBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (4 FLUOROPHENYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 RIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (4 METHOXYBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (4 METHYLBENZYL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A] PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; TERT BUTYL[3 [2 (PYRIDIN 2 YL) HEXAHYDRO 3 OXOIMIDAZO[1,5 A]PYRAZIN 7(8H) YL] 3 OXO 1 (2,4,5 TRIFLUOROBENZYL)PROPYL]CARBAMATE; UNCLASSIFIED DRUG;

ARTICLE; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; IN VITRO STUDY; MOLECULAR DOCKING;

DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DRUG EVALUATION, PRECLINICAL; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; PYRAZINES;

EID: 77957837734     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2010.08.002     Document Type: Article

References (21)

1. http://www.diabetesatlas.org/
2. L.B. Knudsen J. Med. Chem. 47 2004 4128 4134
3. A.E. Weber J. Med. Chem. 47 2004 4135 4141
4. D.J. Drucker Endocrinology 144 2003 5145 5148
5. J.A. Pospisilik, J. Martin, T. Doty, J.A. Ehses, N. Pamir, F.C. Lynn, S. Piteau, H.-U. Demuth, C.H.S. McIntosh, and R.A. Pederson Diabetes 52 2003 741 750
6. T.J. Kieffer, C.H.S. McIntosh, and T.A. Pederson Endocrinology 136 1995 3585 3596
7. C.F. Deacon, M.A. Nauck, M. Toft-Nielson, L. Pridal, B. Willms, and J.J. Holst Diabetes 44 1995 1126 1131
8. Abd A. Tahrani, M.K. Piya, A. Kennedy, and A.H. Barnett Pharmacol. Ther. 125 2010 328 361
9. S.H. Havale, and M. Pal Bioorg. Med. Chem. 17 2009 1783 1802
10. B.T. Srinivasan, J. Jarvis, K. Khunti, and M.J. Davies Postgrad. Med. J. 84 2008 524 531
11. D. Kim, L. Wang, M. Beconi, G.J. Eiermann, M.H. Fisher, H. He, G.J. Hickey, J.E. Kowalchick, B. Leiting, K. Lyons, F. Marsilio, M.E. McCann, R.A. Patel, A. Petrov, G. Scapin, S.B. Patel, R.S. Roy, J.K. Wu, M.J. Wyvratt, B.B. Zhang, L. Zhu, N.A. Thornberry, and A. Weber J. Med. Chem. 48 2005 141 151
12. R. Angelaud, Y. Zhong, P. Maligres, J. Lee, and D. Askin J. Org. Chem. 70 2005 1949 1952
13. K.B. Hansen, J. Balsells, S. Dreher, Y. Hsiao, M. Kubryk, M. Palucki, N. Rivera, D. Steinhuebel, J.D. Armstrong III, D. Askin, and E.J.J. Grabowski Org. Process Res. Dev. 9 2005 634 639
14. J.W.F. Barnick, J.L. Van der Baan, and F. Bickelhaupt Synthesis 1979 787 788
15. Y. Jin, and D.H. Kim Synlett 1998 1189 1190
16. H.-W. Gao, and A. Renslo J. Med. Chem. 72 2007 8591 8592
17. I. Brandt, J. Joossens, X. Chen, M.-B. Maes, S. Scharpé, I. De Meester, and A.M. Lambeir Biochem. Pharmacol. 70 2005 134 143
18. I. De Meester, G. Vanhoof, A.M. Lambeir, and S. Scharpé J. Immunol. Methods 189 1996 99 105
19. H.B. Rasmussen, S. Branner, F.C. Wiberg, and N. Wagtmann Nat. Struct. Biol. 10 2003 19 25
20. Sybyl Molecular Modeling Software Packages; Ver.7.0 2004 TRIPOS, Associates, Inc. St Louis, MO 63144
21. M.L. Verdonk, J.C. Cole, M.J. Hartshorn, C.W. Murray, and R.D. Taylor Proteins 52 2003 609 623