Discovery and optimization of a novel series of pyrazolyltetrahydropyran N-type calcium channel (Cav 2.2) blockers for the treatment of pain

被引：7

作者：

Wall, Mark J. ^{[1
]}

Subasinghe, Nalin L. ^{[1
]}

Winters, Michael P. ^{[1
]}

Lubin, Mary Lou ^{[1
]}

Finley, Michael F. A. ^{[1
]}

Qin, Ning ^{[1
]}

Brandt, Michael R. ^{[1
]}

Neeper, Michael P. ^{[1
]}

Schneider, Craig R. ^{[1
]}

Colburn, Raymond W. ^{[1
]}

Flores, Christopher M. ^{[1
]}

Sui, Zhihua ^{[1
]}

机构：

[1] Janssen Res & Dev LLC, Welsh & McKean Rd, Spring House, PA 19477 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 23-24期

关键词：

Pain; N-type calcium channel; Cav; 2.2; Pyrazoles; CFA model; CCI model; OMEGA-CONOTOXIN;

D O I：

10.1016/j.bmcl.2018.10.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of pyrazolyltetrahydropyran N-type calcium channel blockers are described. Structural modifications of the series led to potent compounds in both a cell-based fluorescent calcium influx assay and a patch clamp electrophysiology assay. Representative compounds from the series were bioavailable and showed efficacy in the rat CFA and CCI models of inflammatory and neuropathic pain.

引用

页码：3780 / 3783

页数：4

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