Synthetic and biological studies of carbasugar SGLT2 inhibitors

Wai Lung Ng, Tony Kung Ming Shing

Research output: Contribution to journalArticle

Abstract

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes. Unfortunately, current therapeutic agents are not so effective that only less than 36% of the patients have been treated satisfactorily. Thus, we set out to investigate novel small-molecule carbohydrate mimics as potential antidiabetic agents to supplement the existing medication. Selective inhibition of the transporter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood glucose level in T2DM patients. We have pioneered the design and synthesis of some novel carbasugars (pseudosugars), readily available from inexpensive D-glu-conolactone, which contains a metabolically stable-pseudo-glycosidic" C-O bond. Their aza-analogues (with a C-N bond) and carbon-analogues (with a C-C bond) have been prepared to provide important insights into the structure-activity relationship (SAR) of these inhibitors, thereby aiding the development of carbasugar SGLT2 inhibitors as potential antidiabetic agents. Our synthetic targets are the carbocyclic analogues of sergliflozin and dapagliflozin, which are readily accessible via various transition metal-catalyzed crosscoupling reactions. We herein describe our novel synthetic approaches towards carbasugar SGLT2 inhibitors, and discuss their SAR.

Original languageEnglish
Pages (from-to)1215-1222
Number of pages8
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume76
Issue number11
DOIs
Publication statusPublished - 2018 Jan 1

ASJC Scopus subject areas

  • Organic Chemistry

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