Glycosylated Dihydrochalcones as Potent and Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors

Bioorg Med Chem Lett. 2004 Oct 18;14(20):5121-5. doi: 10.1016/j.bmcl.2004.07.082.

Abstract

A series of glucose conjugates was synthesized and tested for inhibition of SGLT1 and SGLT2. The core structure was derived from compound 1a. Modification of the benzofuran moiety and 4'-substituent of the phenyl ring in compound 1a improved selectivity at SGLT2. Select compounds were compared to 1a in metabolic stability and in vivo efficacy studies.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cells, Cultured
  • Chalcone / analogs & derivatives*
  • Chalcone / chemical synthesis*
  • Chalcone / pharmacology
  • Chalcones
  • Drug Stability
  • Glycosylation
  • Humans
  • In Vitro Techniques
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Microsomes, Liver / metabolism
  • Monosaccharide Transport Proteins / antagonists & inhibitors*
  • Phlorhizin / chemical synthesis
  • Phlorhizin / pharmacology
  • Rats
  • Rats, Zucker
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Structure-Activity Relationship

Substances

  • Chalcones
  • Membrane Glycoproteins
  • Monosaccharide Transport Proteins
  • SLC5A1 protein, human
  • SLC5A2 protein, human
  • Slc5a1 protein, rat
  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2
  • Chalcone
  • Phlorhizin
  • dihydrochalcone