Synthesis and DP-IV inhibition of cyano-pyrazoline derivatives as potent anti-diabetic agents

A new series of cyano-pyrazoline derivatives with a secondary amine at P-2 site was synthesized through achiral and chiral synthetic methods and evaluated for their ability to inhibit dipeptidyl peptidase IV (DP-IV). Compound 5i revealed good in vivo efficacy (ED50: 4.1 mg/kg; in vivo DP-IV inhibition). Also chiral derivative (11b) having (S)-configuration of compound 5i was found to be more potent. (C) 2004 Elsevier Ltd. All rights reserved.