Evaluation of basic, heterocyclic ring systems as templates for use as potassium competitive acid blockers (pCABs)

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6813-7. doi: 10.1016/j.bmcl.2009.07.002. Epub 2009 Jul 4.

Abstract

A variety of basic, heterocyclic templates has been reported as potassium-competitive, acid pump antagonists. Herein, we report a comparison of potencies of these templates and others to establish which offers the best start point for further systematic optimisation. Modifications were carried out to improve the developability profile of the more potent 1H-pyrrolo[2,3-c]pyridine template, affording molecules with improved overall in vitro characteristics versus the reported clinical candidate AR-H047108, and comparable to the clinically efficacious AZD-0865.

MeSH terms

  • Binding, Competitive
  • Drug Design
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Molecular Structure
  • Proton Pump Inhibitors*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds
  • Proton Pump Inhibitors
  • Pyridines