The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type 2 diabetes

J Deng, L Peng, G Zhang, X Lan, C Li, F Chen…

Index: Deng, Jifeng; Peng, Li; Zhang, Guicheng; Lan, Xiaobing; Li, Chufang; Chen, Fuxin; Zhou, Yayao; Lin, Zuoxian; Chen, Ling; Dai, Renke; Xu, Hongjiang; Yang, Ling; Zhang, Xiquan; Hu, Wenhui European Journal of Medicinal Chemistry, 2011 , vol. 46, # 1 p. 71 - 76

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Citation Number: 28

Abstract

New dipeptidyl peptidase IV inhibitors were designed based on Alogliptin using a scaffold- hopping strategy. All of the compounds constructed on a thienopyrimidine scaffold demonstrated good inhibition and selectivity for DPP-IV. Compound 10d exhibited subnanomolar (IC50= 0.33 nM) DPP-IV inhibitory activity, good in vivo efficacy and an acceptable pharmacokinetic profile. A pharmacokinetic-driven optimization of 10d may ...