Discovery of vinylcycloalkyl-substituted benzimidazole TRPM8 antagonists effective in the treatment of cold allodynia

Raul R Calvo; Sanath K Meegalla; Daniel J Parks; William H Parsons; Shelley K Ballentine; Mary Lou Lubin; Craig Schneider; Raymond W Colburn; Christopher M Flores; Mark R Player

doi:10.1016/j.bmcl.2012.01.060

Discovery of vinylcycloalkyl-substituted benzimidazole TRPM8 antagonists effective in the treatment of cold allodynia

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1903-7. doi: 10.1016/j.bmcl.2012.01.060. Epub 2012 Jan 28.

Authors

Raul R Calvo¹, Sanath K Meegalla, Daniel J Parks, William H Parsons, Shelley K Ballentine, Mary Lou Lubin, Craig Schneider, Raymond W Colburn, Christopher M Flores, Mark R Player

Affiliation

¹ Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.

PMID: 22330635
DOI: 10.1016/j.bmcl.2012.01.060

Abstract

Thermosensitive transient receptor potential melastatin 8 (TRPM8) antagonists are considered to be potential therapeutic agents for the treatment of cold hypersensitivity. The discovery of a new class of TRPM8 antagonists that shows in vivo efficacy in the rat chronic constriction injury (CCI)-induced model of neuropathic pain is described.

MeSH terms

Analgesics / chemistry*
Analgesics / pharmacokinetics
Analgesics / pharmacology
Analgesics / therapeutic use*
Animals
Benzimidazoles / chemistry*
Benzimidazoles / pharmacokinetics
Benzimidazoles / pharmacology
Benzimidazoles / therapeutic use*
Cold Temperature
Dogs
HEK293 Cells
Humans
Hyperalgesia / drug therapy*
Neuralgia / drug therapy*
Rats
TRPM Cation Channels / antagonists & inhibitors*
TRPM Cation Channels / metabolism

Substances

Analgesics
Benzimidazoles
TRPM Cation Channels
TRPM8 protein, human
Trpm8 protein, rat
benzimidazole