Optimization of triazoles as novel and potent nonphlorizin SGLT2 inhibitors

Xiaohui Du; Mike Lizarzaburu; Simon Turcotte; Taeweon Lee; Joanne Greenberg; Bei Shan; Peter Fan; Yun Ling; Julio C Medina; Jonathan Houze

doi:10.1016/j.bmcl.2011.04.053

Optimization of triazoles as novel and potent nonphlorizin SGLT2 inhibitors

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3774-9. doi: 10.1016/j.bmcl.2011.04.053. Epub 2011 Apr 20.

Authors

Xiaohui Du¹, Mike Lizarzaburu, Simon Turcotte, Taeweon Lee, Joanne Greenberg, Bei Shan, Peter Fan, Yun Ling, Julio C Medina, Jonathan Houze

Affiliation

¹ Amgen Inc., South San Francisco, CA 94080, USA. xdu@amgen.com

PMID: 21565497
DOI: 10.1016/j.bmcl.2011.04.053

Abstract

Previous efforts have led to the identification of a potent, selective, and nonphlorizin based SGLT2 inhibitor 1. This Letter describes efforts to further optimize the potency, microsomal stability, solubility and pharmacokinetic properties of this series of SGLT2 inhibitors. From these efforts, compounds 28 and 32 have improved solubility and pharmacokinetic properties compared to compound 1.

MeSH terms

Drug Stability
Molecular Structure
Phlorhizin / chemistry
Solubility
Structure-Activity Relationship
Triazoles / chemical synthesis*
Triazoles / chemistry

Substances

Triazoles
Phlorhizin