A potent and selective indole N-type calcium channel (Ca(v)2.2) blocker for the treatment of pain

Sriram Tyagarajan; Prasun K Chakravarty; Min Park; Bishan Zhou; James B Herrington; Kevin Ratliff; Randall M Bugianesi; Brande Williams; Rodolfo J Haedo; Andrew M Swensen; Vivien A Warren; McHardy Smith; Maria Garcia; Gregory J Kaczorowski; Owen B McManus; Kathryn A Lyons; Xiaohua Li; Maria Madeira; Bindhu Karanam; Mitchell Green; Michael J Forrest; Catherine Abbadie; Erin McGowan; Shruti Mistry; Nina Jochnowitz; Joseph L Duffy

doi:10.1016/j.bmcl.2010.11.067

A potent and selective indole N-type calcium channel (Ca(v)2.2) blocker for the treatment of pain

Bioorg Med Chem Lett. 2011 Jan 15;21(2):869-73. doi: 10.1016/j.bmcl.2010.11.067. Epub 2010 Nov 21.

Affiliation

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

PMID: 21195616
DOI: 10.1016/j.bmcl.2010.11.067

Abstract

N-type calcium channels (Ca(v)2.2) have been shown to play a critical role in pain. A series of low molecular weight 2-aryl indoles were identified as potent Ca(v)2.2 blockers with good in vitro and in vivo potency.

MeSH terms

Animals
Calcium Channel Blockers / pharmacokinetics
Calcium Channel Blockers / pharmacology
Calcium Channel Blockers / therapeutic use*
Calcium Channels, N-Type / metabolism*
Dogs
Haplorhini
Humans
Indoles / pharmacokinetics
Indoles / pharmacology
Indoles / therapeutic use*
Pain / drug therapy*
Rats

Substances

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