Bioorganic & Medicinal Chemistry Letters 2006-06-15

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

Ting-Yueh Tsai, Mohane Selvaraj Coumar, Tsu Hsu, Hsing-Pang Hsieh, Chia-Hui Chien, Chiung-Tong Chen, Chung-Nien Chang, Yu-Kang Lo, Ssu-Hui Wu, Chung-Yu Huang, Yu-Wen Huang, Min-Hsien Wang, Hsin-Yi Wu, Hong-Jen Lee, Xin Chen, Yu-Sheng Chao, Weir-Torn Jiaang

Index: Bioorg. Med. Chem. Lett. 16(12) , 3268-72, (2006)

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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.