Design, synthesis, and biological evaluation of aryl N-methoxyamide derivatives as GPR119 agonists

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3909-3914. doi: 10.1016/j.bmcl.2017.06.032. Epub 2017 Jun 13.

Abstract

A series of N-methoxyamide derivatives was identified and evaluated as GPR119 agonists. Several N-methoxyamides with thienopyrimidine and pyridine scaffolds showed potent GPR119 agonistic activities. Among them, compound 9c displayed good in vitro activity and potency. Moreover, compound 9c lowered glucose excursion in mice in an oral glucose tolerance test and increased GLP-1 secretion in intestinal cells.

Keywords: Diabetes; GPR119; N-methoxyamide derivative; Treatment.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose / administration & dosage
  • Glucose Tolerance Test
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestines / cytology
  • Intestines / drug effects
  • Mice
  • Molecular Structure
  • Receptors, G-Protein-Coupled / agonists*
  • Structure-Activity Relationship

Substances

  • Amides
  • GPR119 protein, human
  • Receptors, G-Protein-Coupled
  • Glucagon-Like Peptide 1
  • Glucose