Substituted pyrrolidine-2,4-dicarboxylic acid amides as potent dipeptidyl peptidase IV inhibitors

[[abstract]]A series of substituted pyrrolidine-2,4-dicarboxylic acid amides were synthesized as potential antidiabetic agents, and many of them showed good in vitro DPP-IV inhibition (IC50 = 2-250 nM) with selectivity over DPP-II, DPP8, and FAP enzymes. Selected compounds 8c and 11a showed in vivo plasma DPP-IV inhibition after oral administration in Wistar rats. (c) 2006 Elsevier Ltd. All rights reserved