Referenced in: HCN1

Automatically associated channels: HCN1

Title: Discovery of a novel series of selective HCN1 blockers.

Authors: Kelly J McClure, Michael Maher, Nancy Wu, Sandra R Chaplan, William A Eckert, Dong H Lee, Alan D Wickenden, Michelle Hermann, Brett Allison, Natalie Hawryluk, J Guy Breitenbucher, Cheryl A Grice

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Sep 15 , 21, 5197-201

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21824780

Abstract
The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1. Optimization of this hit led to the identification of the potent, 1,1-disubstituted cyclohexane HCN1 blocker, 2-ethoxy-N-((1-(4-isopropylpiperazin-1-yl)cyclohexyl)methyl)benzamide. The work leading to the discovery of this compound is described herein.