The search for novel TRPV1-antagonists: from carboxamides to benzimidazoles and indazolones

Stephen Robert Fletcher; Edward McIver; Stephen Lewis; Frank Burkamp; Clare Leech; Glenn Mason; Susan Boyce; Denise Morrison; Gillian Richards; Kathy Sutton; Anthony Brian Jones

doi:10.1016/j.bmcl.2006.03.004

The search for novel TRPV1-antagonists: from carboxamides to benzimidazoles and indazolones

Bioorg Med Chem Lett. 2006 Jun 1;16(11):2872-6. doi: 10.1016/j.bmcl.2006.03.004. Epub 2006 Mar 24.

Authors

Stephen Robert Fletcher¹, Edward McIver, Stephen Lewis, Frank Burkamp, Clare Leech, Glenn Mason, Susan Boyce, Denise Morrison, Gillian Richards, Kathy Sutton, Anthony Brian Jones

Affiliation

¹ Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. stephen_fletcher@merck.com

PMID: 16563760
DOI: 10.1016/j.bmcl.2006.03.004

Abstract

Based on a series of diaryl amides the corresponding inverse amides have been found to be potent TRPV1 receptor antagonists. Benzimidazole and indazolone derivatives prepared retained good potency in vitro and indazolone 4a was identified as a novel TRPV1 receptor antagonist suitable for evaluating orally in animal models of analgesia.

MeSH terms

Amines / chemistry
Benzimidazoles / chemical synthesis
Benzimidazoles / chemistry*
Benzimidazoles / pharmacology*
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry*
Imidazoles / pharmacology*
Molecular Structure
Structure-Activity Relationship
TRPV Cation Channels / antagonists & inhibitors*
TRPV Cation Channels / metabolism

Substances

Amines
Benzimidazoles
Imidazoles
TRPV Cation Channels
TRPV1 protein, human
benzimidazole