Discovery of Potent and Selective Dipeptidyl Peptidase IV Inhibitors Derived from β-Aminoamides Bearing Subsituted Triazolopiperazines†

…, GJ Eiermann, MH Fisher, H He, B Leiting…

Index: Kim, Dooseop; Kowalchick, Jennifer E.; Brockunier, Linda L.; Parmee, Emma R.; Eiermann, George J.; Fisher, Michael H.; He, Huaibing; Leiting, Barbara; Lyons, Kathryn; Scapin, Giovanna; Patel, Sangita B.; Petrov, Aleksandr; Pryor, Kelly Ann D.; Roy, Ranabir Sinha; Wu, Joseph K.; Zhang, Xiaoping; Wyvratt, Matthew J.; Zhang, Bei B.; Zhu, Lan; Thornberry, Nancy A.; Weber, Ann E. Journal of Medicinal Chemistry, 2008 , vol. 51, # 3 p. 589 - 602

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Citation Number: 48

Abstract

A series of β-aminoamides bearing triazolopiperazines have been discovered as potent, selective, and orally active dipeptidyl peptidase IV (DPP-4) inhibitors by extensive structure– activity relationship (SAR) studies around the triazolopiperazine moiety. Among these, compound 34b with excellent in vitro potency (IC50= 4.3 nM) against DPP-4, high selectivity over other enzymes, and good pharmacokinetic profiles exhibited pronounced in vivo ...