Document Report Card

ID: ALA1143002

Journal: J Med Chem

Title: Discovery and structure-activity relationships of piperidinone- and piperidine-constrained phenethylamines as novel, potent, and selective dipeptidyl peptidase IV inhibitors.

Authors: Pei Z, Li X, von Geldern TW, Longenecker K, Pireh D, Stewart KD, Backes BJ, Lai C, Lubben TH, Ballaron SJ, Beno DW, Kempf-Grote AJ, Sham HL, Trevillyan JM.

Abstract: Dipeptidyl peptidase IV (DPP4) inhibitors are emerging as a new class of therapeutic agents for the treatment of type 2 diabetes. They exert their beneficial effects by increasing the levels of active glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are two important incretins for glucose homeostasis. Starting from a high-throughput screening hit, we were able to identify a series of piperidinone- and piperidine-constrained phenethylamines as novel DPP4 inhibitors. Optimized compounds are potent, selective, and have good pharmacokinetic profiles.

CiteXplore: 17367123

DOI: 10.1021/jm061436d