Discovery and optimization of arylsulfonyl 3-(pyridin-2-yloxy)anilines as novel GPR119 agonists

Bioorg Med Chem Lett. 2013 Jun 15;23(12):3609-13. doi: 10.1016/j.bmcl.2013.04.014. Epub 2013 Apr 15.

Abstract

We describe the discovery of a series of arylsulfonyl 3-(pyridin-2-yloxy)anilines as GPR119 agonists derived from compound 1. Replacement of the three methyl groups in 1 with metabolically stable moieties led to the identification of compound 34, a potent and efficacious GPR119 agonist with improved pharmacokinetic (PK) properties.

Publication types

  • Letter

MeSH terms

  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry*
  • Aniline Compounds / pharmacology*
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Discovery
  • Humans
  • Mice
  • Models, Molecular
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • GPR119 protein, human
  • Receptors, G-Protein-Coupled