Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine acid pump antagonists (APAs)

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3602-6. doi: 10.1016/j.bmcl.2009.04.127. Epub 2009 May 3.

Abstract

Acid pump antagonists (APAs) such as the imidazo[1,2-a]pyridine AZD-0865 2 have proven efficacious at low oral doses in acid related gastric disorders. Herein we describe some of the broader SAR in this class of molecule and detail the discovery of an imidazo[1,2-a]pyridine 15 which has excellent efficacy in animal models of gastric acid secretion following oral administration, as well as a good overall developability profile. The discovery strategy focuses on use of heteroaryl and heterocyclic substituents at the C-6 position and optimization of developability characteristics through modulation of global physico-chemical properties.

MeSH terms

  • Administration, Oral
  • Animals
  • Dogs
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Proton Pump Inhibitors* / chemical synthesis
  • Proton Pump Inhibitors* / chemistry*
  • Proton Pump Inhibitors* / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Proton Pump Inhibitors
  • Pyridines
  • H(+)-K(+)-Exchanging ATPase
  • imidazo(1,2-a)pyridine