(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: A Selective α-Amino Amide Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes

Citations Over TimeTop 10% of 2006 papers

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.

Related Papers

• → Dipeptidyl peptidase IV (DPP-IV) inhibitory properties of a camel whey protein enriched hydrolysate preparation(2018)118 cited
• → Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism(2016)58 cited
• → Ameliorating effect of the novel dipeptidyl peptidase‐4 inhibitor teneligliptin on psoriasis: A report of two cases(2015)18 cited
• → K579, a slow-binding inhibitor of dipeptidyl peptidase IV, is a long-acting hypoglycemic agent(2004)32 cited
• → The activity of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice immunized with type II collagen(1992)