| Literature DB >> 15634008 |
Dooseop Kim1, Liping Wang, Maria Beconi, George J Eiermann, Michael H Fisher, Huaibing He, Gerard J Hickey, Jennifer E Kowalchick, Barbara Leiting, Kathryn Lyons, Frank Marsilio, Margaret E McCann, Reshma A Patel, Aleksandr Petrov, Giovanna Scapin, Sangita B Patel, Ranabir Sinha Roy, Joseph K Wu, Matthew J Wyvratt, Bei B Zhang, Lan Zhu, Nancy A Thornberry, Ann E Weber.
Abstract
A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC(50) = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.Entities:
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Year: 2005 PMID： 15634008 DOI： 10.1021/jm0493156
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446