Structure Report for: 2OQI

Pei, Z., Li, X., von Geldern, T. W., Longenecker, K.L., Pireh, D., Stewart, K.D., Backes, B.J., Lai, C., Lubben, T.H., Ballaron, S.J., Beno, D.W., Kempf-Grote, A.J., Sham, H.L., Trevillyan, J.M.

Title: Discovery and structure-activity relationships of piperidinone- and piperidine-constrained phenethylamines as novel, potent, and selective dipeptidyl peptidase IV inhibitors
Pei Z, Li X, von Geldern TW, Longenecker K, Pireh D, Stewart KD, Backes BJ, Lai C, Lubben TH and Trevillyan JM <4 more author(s)> 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 (- 4)
Ref: Journal of Medicinal Chemistry, 50:1983, 2007 : PubMed
Abstract


ESTHER: Pei_2007_J.Med.Chem_50_1983
PubMedSearch: Pei 2007 J.Med.Chem 50 1983
PubMedID: 17367123
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: Piperidinone-constrained-phenethylamine-31, Piperidine-constrained-phenethylamine-42

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.