Referenced in: none

Automatically associated channels: Kv11.1

Title: Discovery and hit-to-lead optimization of pyrrolopyrimidines as potent, state-dependent Na(v)1.7 antagonists.

Authors: Nagasree Chakka, Howie Bregman, Bingfan Du, Hanh Nho Nguyen, John L Buchanan, Elma Feric, Joseph Ligutti, Dong Liu, Jeff S McDermott, Anruo Zou, Stefan I McDonough, Erin F DiMauro

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Mar 1 , 22, 2052-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22318156

Abstract
Herein we describe the discovery, optimization, and structure-activity relationships of novel potent pyrrolopyrimidine Na(v)1.7 antagonists. Hit-to-lead SAR studies of the pyrrolopyrimidine core, head, and tail groups of the molecule led to the identification of pyrrolopyrimidine 48 as exceptionally potent Na(v)1.7 blocker with good selectivity over hERG and improved microsomal stability relative to our hit molecule and pyrazolopyrimidine 8 as a promising starting point for future optimization efforts.