Synthetic and biological studies of carbasugar SGLT2 inhibitors

Wai Lung Ng, Tony K.M. Shing

研究成果: Article査読

3 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1215-1222
ページ数8
ジャーナルYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
76
11
DOI
出版ステータスPublished - 2018

ASJC Scopus subject areas

  • 有機化学

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