Discovery of a novel class of biphenyl pyrazole sodium channel blockers for treatment of neuropathic pain

Sriram Tyagarajan; Prasun K Chakravarty; Bishan Zhou; Brett Taylor; Ronsar Eid; Michael H Fisher; William H Parsons; Mathew J Wyvratt; Kathryn A Lyons; Tracy Klatt; Xiaohua Li; Sanjeev Kumar; Brande Williams; John Felix; Birgit T Priest; Richard M Brochu; Vivien Warren; McHardy Smith; Maria Garcia; Gregory J Kaczorowski; William J Martin; Catherine Abbadie; Erin McGowan; Nina Jochnowitz; Ann Weber; Joseph L Duffy

doi:10.1016/j.bmcl.2010.10.017

Discovery of a novel class of biphenyl pyrazole sodium channel blockers for treatment of neuropathic pain

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7479-82. doi: 10.1016/j.bmcl.2010.10.017. Epub 2010 Oct 14.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. sriram_tyagarajan@merck.com

PMID: 21106456
DOI: 10.1016/j.bmcl.2010.10.017

Abstract

A series of novel biphenyl pyrazole dicarboxamides were identified as potential sodium channel blockers for treatment of neuropathic pain. Compound 20 had outstanding efficacy in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain.

MeSH terms

Animals
Biphenyl Compounds / chemical synthesis
Biphenyl Compounds / chemistry*
Biphenyl Compounds / therapeutic use
Dogs
Drug Evaluation, Preclinical
Humans
Mice
Microsomes, Liver / metabolism
Motor Activity / drug effects
Neuralgia / drug therapy*
Pyrazoles / chemistry*
Pyrazoles / pharmacokinetics
Pyrazoles / therapeutic use
Rats
Sodium Channel Blockers / chemistry*
Sodium Channel Blockers / pharmacokinetics
Sodium Channel Blockers / therapeutic use
Sodium Channels / chemistry*
Sodium Channels / metabolism

Substances

Biphenyl Compounds
Pyrazoles
Sodium Channel Blockers
Sodium Channels