Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors

Synthesis and pharmacological characterization of potent, selective, and orally bioavailable isoindoline class dipeptidyl peptidase IV inhibitors

BMC Chemistry, September 2011

22373386

Noriyasu Kato, Mitsuru Oka, Takayo Murase, Masahiro Yoshida, Masao Sakairi, Mirensha Yakufu, Satoko Yamashita, Yoshika Yasuda, Aya Yoshikawa, Yuji Hayashi, Masahiro Shirai, Yukie Mizuno, Mitsuaki Takeuchi, Mitsuhiro Makino, Motohiro Takeda, Takuji Kakigami

Focused structure-activity relationships of isoindoline class DPP-IV inhibitors have led to the discovery of 4b as a highly selective, potent inhibitor of DPP-IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the strongly active metabolite 4l in high yield, resulting in good in vivo efficacy for antihyperglycemic activity.