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Discovery of a novel series of selective HCN1 blockers.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

McClure KJ,Maher M,Wu N,Chaplan SR,Eckert WA 3rd,Lee DH,Wickenden AD,Hermann M,Allison B,Hawryluk N,Breitenbucher JG,Grice CA

doi

10.1016/j.bmcl.2011.07.051

subject

Has Abstract

pub_date

2011-09-15 00:00:00

pages

5197-201

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00989-9

journal_volume

21

pub_type

杂志文章

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