Referenced in: none

Automatically associated channels: Kv11.1

Title: The discovery of aminopyrazines as novel, potent Na(v)1.7 antagonists: hit-to-lead identification and SAR.

Authors: Howard Bregman, Hanh Nho Nguyen, Elma Feric, Joseph Ligutti, Dong Liu, Jeff S McDermott, Ben Wilenkin, Anruo Zou, Liyue Huang, Xingwen Li, Stefan I McDonough, Erin F DiMauro

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Mar 1 , 22, 2033-42

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22306122

Abstract
Herein the discovery of a novel class of aminoheterocyclic Na(v)1.7 antagonists is reported. Hit compound 1 was potent but suffered from poor pharmacokinetics and selectivity. The compact structure of 1 offered a modular synthetic strategy towards a broad structure-activity relationship analysis. This analysis led to the identification of aminopyrazine 41, which had vastly improved hERG selectivity and pharmacokinetic properties.