Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group |
| |
Authors: | Kondo Takashi Nekado Takahiro Sugimoto Isamu Ochi Kenya Takai Shigeyuki Kinoshita Atsushi Hatayama Akira Yamamoto Susumu Kishikawa Katsuya Nakai Hisao Toda Masaaki |
| |
Affiliation: | Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. t.kondou@ono.co.jp |
| |
Abstract: | A series of (4beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|