The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.
Basic Information
ID: ALA3804801
Journal: Bioorg Med Chem Lett
Title: The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.
Authors: Cox JM, Chu HD, Kuethe JT, Gao YD, Scapin G, Eiermann G, He H, Li X, Lyons KA, Metzger J, Petrov A, Wu JK, Xu S, Sinha-Roy R, Weber AE, Biftu T.
Abstract: Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans.
CiteXplore: 27106708
DOI: 10.1016/j.bmcl.2016.04.020
Patent ID: ┄