Author/Authors :
Mohane Selvaraj Coumar، نويسنده , , Chung-Nien Chang، نويسنده , , Chiung-Tong Chen، نويسنده , , Xin Chen، نويسنده , , Chia-Hui Chien، نويسنده , , Ting-Yueh Tsai، نويسنده , , Jai-Hong Cheng، نويسنده , , Hsin-Yi Wu، نويسنده , , Chia-Hung Han، نويسنده , , Ssu-Hui Wu، نويسنده , , Yu-Wen Huang، نويسنده , , Tsu Hsu، نويسنده , , Li-Jen Hsu، نويسنده , , Yu-Sheng Chao، نويسنده , , Hsing-Pang Hsieh، نويسنده , , Weir-Torn Jiaang، نويسنده ,
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.
