Discovery of potent dipeptidyl peptidase IV inhibitors derived from β-aminoamides bearing substituted [1,2,3]-triazolopiperidines for the treatment of type 2 diabetes

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1731-5. doi: 10.1016/j.bmcl.2011.01.086. Epub 2011 Jan 22.

Abstract

A series of novel [1,2,3]-triazolopiperidine derivatives 5a-5y were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes, most of the compounds exhibited excellent in vitro potency (IC(50)<50n M) against DPP-4. Among these, compound 5d with potent in vitro activity against DPP-4 and good pharmacokinetic profiles exhibited pronounced in vivo efficacy in an oral glucose tolerance test (OGTT) in ICR mice. On the base of these properties, compound 5d was selected as a potential new candidate for the treatment of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / isolation & purification
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Discovery
  • Inhibitory Concentration 50
  • Mice
  • Mice, Inbred ICR
  • Piperidines / isolation & purification
  • Piperidines / therapeutic use*

Substances

  • Amides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Piperidines