(3R)-4-[(3R)-3-Amino-4-(2, 4, 5-trifluorophenyl) butanoyl]-3-(2, 2, 2-trifluoroethyl)-1, 4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of …

…, B Leiting, K Lyons, A Petrov, R Sinha-Roy…

Index: Biftu, Tesfaye; Feng, Dennis; Qian, Xiaoxia; Liang, Gui-Bai; Kieczykowski, Gerard; Eiermann, George; He, Huaibing; Leiting, Barbara; Lyons, Kathy; Petrov, Aleksandr; Sinha-Roy, Ranabir; Zhang, Bei; Scapin, Giovanna; Patel, Sangita; Gao, Ying-Duo; Singh, Suresh; Wu, Joseph; Zhang, Xiaoping; Thornberry, Nancy A.; Weber, Ann E. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 1 p. 49 - 52

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Citation Number: 39

Abstract

Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC50= 18nM) with 3-(2, 2, 2- trifluoroethyl)-1, 4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC50= 2.6 nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.