2. Academic Validation
  3. 5a-Carba-β-D-glucopyranose derivatives as novel sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes

5a-Carba-β-D-glucopyranose derivatives as novel sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes

  • Bioorg Med Chem. 2011 Sep 15;19(18):5334-41. doi: 10.1016/j.bmc.2011.08.005.
Yoshihito Ohtake 1,  Tsutomu Sato,  Hiroharu Matsuoka,  Masahiro Nishimoto,  Naoki Taka,  Koji Takano,  Keisuke Yamamoto,  Masayuki Ohmori,  Takashi Higuchi,  Masatoshi Murakata,  Takamitsu Kobayashi,  Kazumi Morikawa,  Nobuo Shimma,  Masayuki Suzuki,  Hitoshi Hagita,  Kazuharu Ozawa,  Koji Yamaguchi,  Motohiro Kato,  Sachiya Ikeda
Affiliations

Affiliation

  • 1 Research Division, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. ohtakeysh@chugai-pharm.co.jp
PMID: 21873071 DOI: 10.1016/j.bmc.2011.08.005
Abstract

5a-Carba-β-D-glucopyranose derivatives were synthesized and identified as novel SGLT2-selective inhibitors. These inhibitors exhibited potent SGLT2 inhibition with high selectivity over SGLT1. Among the tested compounds, 6f indicated the most potent hSGLT2 inhibition and the highest selectivity over hSGLT1. Moreover, the pharmacokinetics data also showed that 6h, which had the same aglycon structure as sergliflozin-active (3-active), had a threefold longer half-life time (T(1/2)) than sergliflozin (3) with a high distribution volume in db/db mice. Subsequently, 6h lowered blood glucose levels as much as 3 and showed longer hypoglycemic action than 3 in db/db mice.

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