Discovery and SAR of a novel series of 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles as N-type calcium channel inhibitors

Michael P Winters; Nalin Subasinghe; Mark Wall; Edward Beck; Michael R Brandt; Michael F A Finley; Yi Liu; Mary Lou Lubin; Michael P Neeper; Ning Qin; Christopher M Flores; Zhihua Sui

doi:10.1016/j.bmcl.2014.03.063

Discovery and SAR of a novel series of 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles as N-type calcium channel inhibitors

Bioorg Med Chem Lett. 2014 May 1;24(9):2057-61. doi: 10.1016/j.bmcl.2014.03.063. Epub 2014 Mar 28.

Affiliations

¹ Janssen Research and Development, LLC, 1400 McKean Rd., Spring House, PA 19477, USA. Electronic address: mwinter4@its.jnj.com.
² Janssen Research and Development, LLC, 1400 McKean Rd., Spring House, PA 19477, USA.

PMID: 24726803
DOI: 10.1016/j.bmcl.2014.03.063

Abstract

A novel series of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles were investigated as N-type calcium channel blockers (Cav2.2 channels), a chronic pain target. One compound was active in vivo in the rat CFA pain model.

Keywords: 2,4,5,6-Tetrahydrocyclopenta[c]pyrazoles; Ca(v)2.2 blockers; N-type calcium channel; Pain; Rat CFA model.

MeSH terms

Analgesics / chemistry*
Analgesics / metabolism
Analgesics / pharmacokinetics
Analgesics / pharmacology*
Animals
Calcium Channel Blockers / chemistry*
Calcium Channel Blockers / metabolism
Calcium Channel Blockers / pharmacokinetics
Calcium Channel Blockers / pharmacology*
Calcium Channels, N-Type / metabolism*
Microsomes, Liver / metabolism
Pain / drug therapy
Pyrazoles / chemistry*
Pyrazoles / metabolism
Pyrazoles / pharmacokinetics
Pyrazoles / pharmacology*
Rats

Substances

Analgesics
Cacna1b protein, rat
Calcium Channel Blockers
Calcium Channels, N-Type
Pyrazoles