2. Academic Validation
  3. Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes

Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes

  • J Med Chem. 2012 Sep 13;55(17):7828-40. doi: 10.1021/jm300884k.
Yoshihito Ohtake 1,  Tsutomu Sato,  Takamitsu Kobayashi,  Masahiro Nishimoto,  Naoki Taka,  Koji Takano,  Keisuke Yamamoto,  Masayuki Ohmori,  Marina Yamaguchi,  Kyoko Takami,  Sang-Yong Yeu,  Koo-Hyeon Ahn,  Hiroharu Matsuoka,  Kazumi Morikawa,  Masayuki Suzuki,  Hitoshi Hagita,  Kazuharu Ozawa,  Koji Yamaguchi,  Motohiro Kato,  Sachiya Ikeda
Affiliations

Affiliation

  • 1 Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. ohtakeysh@chugai-pharm.co.jp
PMID: 22889351 DOI: 10.1021/jm300884k
Abstract

Inhibition of sodium glucose cotransporter 2 (SGLT2) has been proposed as a novel therapeutic approach to treat type 2 diabetes. In our efforts to discover novel inhibitors of SGLT2, we first generated a 3D pharmacophore model based on the superposition of known inhibitors. A search of the Cambridge Structural Database using a series of pharmacophore queries led to the discovery of an O-spiroketal C-arylglucoside scaffold. Subsequent chemical examination combined with computational modeling resulted in the identification of the clinical candidate 16d (CSG452, tofogliflozin), which is currently under phase III clinical trials.

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