3-[2-((2S)-2-cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramide analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes |
| |
Authors: | Coumar Mohane Selvaraj Chang Chung-Nien Chen Chiung-Tong Chen Xin Chien Chia-Hui Tsai Ting-Yueh Cheng Jai-Hong Wu Hsin-Yi Han Chia-Hung Wu Ssu-Hui Huang Yu-Wen Hsu Tsu Hsu Li-Jen Chao Yu-Sheng Hsieh Hsing-Pang Jiaang Weir-Torn |
| |
Affiliation: | Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan, ROC. |
| |
Abstract: | Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM) has the potential for development as antidiabetic agent. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|