| Literature DB >> 16759103 |
Scott D Edmondson1, Anthony Mastracchio, Robert J Mathvink, Jiafang He, Bart Harper, You-Jung Park, Maria Beconi, Jerry Di Salvo, George J Eiermann, Huaibing He, Barbara Leiting, Joseph F Leone, Dorothy A Levorse, Kathryn Lyons, Reshma A Patel, Sangita B Patel, Aleksandr Petrov, Giovanna Scapin, Jackie Shang, Ranabir Sinha Roy, Aaron Smith, Joseph K Wu, Shiyao Xu, Bing Zhu, Nancy A Thornberry, Ann E Weber.
Abstract
A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.Entities:
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Year: 2006 PMID： 16759103 DOI： 10.1021/jm060015t
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446