Discovery and SAR of novel tetrahydropyrrolo[3,4-c]pyrazoles as inhibitors of the N-type calcium channel

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.2014.03.062

Discovery and SAR of novel tetrahydropyrrolo[3,4-c]pyrazoles as inhibitors of the N-type calcium channel

Bioorg Med Chem Lett. 2014 May 1;24(9):2053-6. doi: 10.1016/j.bmcl.2014.03.062. Epub 2014 Mar 27.

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: 24726802
DOI: 10.1016/j.bmcl.2014.03.062

Abstract

A novel series of substituted tetrahydropyrrolo[3,4-c]pyrazoles were investigated as blockers of the N-type calcium channel (Cav2.2 channels), a chronic pain target.

Keywords: Ca(v)2.2 blockers; N-type calcium channel; Pain; Tetrahydropyrrolo[3,4-c]pyrazoles.

MeSH terms

Animals
Calcium Channel Blockers / chemistry*
Calcium Channel Blockers / metabolism
Calcium Channel Blockers / pharmacology*
Calcium Channels, N-Type / metabolism*
Chronic Pain / drug therapy
Humans
Microsomes, Liver / metabolism
Pyrazoles / chemistry*
Pyrazoles / metabolism
Pyrazoles / pharmacology*
Rats
Structure-Activity Relationship

Substances

CACNA1B protein, human
Calcium Channel Blockers
Calcium Channels, N-Type
Pyrazoles