Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus

  • J Med Chem. 2010 Sep 9;53(17):6355-60. doi: 10.1021/jm100332n.
Sumihiro Nomura  1 ,  Shigeki Sakamaki ,  Mitsuya Hongu ,  Eiji Kawanishi ,  Yuichi Koga ,  Toshiaki Sakamoto ,  Yasuo Yamamoto ,  Kiichiro Ueta ,  Hirotaka Kimata ,  Keiko Nakayama ,  Minoru Tsuda-Tsukimoto
Affiliations
  • 1. Medicinal Chemistry Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama, Japan. [email protected]
PMID: 20690635 DOI: 10.1021/jm100332n
Abstract

We discovered that C-glucosides 4 bearing a heteroaromatic ring formed metabolically more stable inhibitors for sodium-dependent glucose cotransporter 2 (SGLT2) than the O-glucoside, 2 (T-1095). A novel thiophene derivative 4b-3 (canagliflozin) was a highly potent and selective SGLT2 Inhibitor and showed pronounced anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice.