Discovery of remogliflozin etabonate: A potent and highly selective SGLT2 inhibitor

Bioorg Med Chem. 2021 Mar 15:34:116033. doi: 10.1016/j.bmc.2021.116033. Epub 2021 Jan 22.

Abstract

We optimized the structure of an active metabolite (1) of WAY-123783, which was obtained from mouse urine after oral administration, to improve selectivity for SGLT2 and oral bioavailability. O-glucoside derivative 24 (remogliflozin etabonate) was subsequently identified as a potent, highly selective, and orally available SGLT2 inhibitor.

Keywords: O-glucoside; Remogliflozin etabonate; SGLT2 inhibitor; Type 2 diabetes mellitus.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • COS Cells
  • Chlorocebus aethiops
  • Drug Discovery
  • Glucosides / chemistry*
  • Glucosides / pharmacology*
  • Glycosuria
  • Mice
  • Molecular Structure
  • Pyrazoles / chemistry*
  • Pyrazoles / metabolism
  • Pyrazoles / pharmacology*
  • Sodium-Glucose Transporter 2 / genetics
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / chemistry*
  • Sodium-Glucose Transporter 2 Inhibitors / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*

Substances

  • Glucosides
  • Pyrazoles
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • WAY 123783
  • remogliflozin etabonate