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Bioorg Med Chem. 2011 Sep 15;19(18):5334-41. doi: 10.1016/j.bmc.2011.08.005. Epub 2011 Aug 8.

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

Author information

1
Research Division, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. ohtakeysh@chugai-pharm.co.jp

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.

PMID:
21873071
DOI:
10.1016/j.bmc.2011.08.005
[Indexed for MEDLINE]

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