Discovery of Ipragliflozin (ASP1941): A novel C-glucoside with benzothiophene structure as a potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus

详细信息	查看全文 | 推荐本文 |

• 作者：Masakazu Imamura^a ; ^{masakazu.imamura@astellas.com} ; Keita Nakanishi^a ; Takayuki Suzuki^a ; Kazuhiro Ikegai^a ; Ryota Shiraki^a ; Takashi Ogiyama^a ; Takeshi Murakami^a ; Eiji Kurosaki^a ; Atsushi Noda^b ; Yoshinori Kobayashi^b ; Masayuki Yokota^b ; Tomokazu Koide^b ; Kazuhiro Kosakai^b ; Yasufumi Ohkura^b ; Makoto Takeuchi^a ; Hiroshi Tomiyama^b ; Mitsuaki Ohta^a
• 关键词：Diabetes ; SGLT2 inhibitor ; Benzothiophene ; Ipragliflozin
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 May, 2012
• 卷：20
• 期：10
• 页码：3263-3279
• 文件大小：1150 K

摘要

A series of C-glucosides with various heteroaromatics has been synthesized and its inhibitory activity toward SGLTs was evaluated. Upon screening several compounds, the benzothiophene derivative (14a) was found to have potent inhibitory activity against SGLT2 and good selectivity versus SGLT1. Through further optimization of 14a, a novel benzothiophene derivative (14h; ipragliflozin, ASP1941) was discovered as a highly potent and selective SGLT2 inhibitor that reduced blood glucose levels in a dose-dependent manner in diabetic models KK-A^y mice and STZ rats.