Discovery of pyrrolo-benzo-1,4-diazines as potent Nav1.7 sodium channel blockers

被引：11
|
作者：
Ho, Ginny D. [1 ]
Tulshian, Deen [1 ]
Bercovici, Ana [1 ]
Tan, Zheng [1 ]
Hanisak, Jennifer [1 ]
Brumfield, Stephanie [1 ]
Matasi, Julius [1 ]
Heap, Charles R. [2 ]
Earley, William G. [2 ]
Courneya, Brandy [2 ]
Herr, R. Jason [2 ]
Zhou, Xiaoping [3 ]
Bridal, Terry [4 ]
Rindgen, Diane [5 ]
Sorota, Steve [4 ]
Yang, Shu-Wei [1 ]
机构：
[1] Merck Res Lab, Discovery Chem, Kenilworth, NJ 07033 USA
[2] AMRI Global, Dept Med Chem, Albany, NY 12203 USA
[3] Merck Res Lab, In Vivo Pharmacol Grp, Kenilworth, NJ 07033 USA
[4] Merck Res Lab, Cardiorenal Grp, Kenilworth, NJ 07033 USA
[5] Merck Res Lab, Pharmacokinet Pharmacodynam & Drug Metab, Kenilworth, NJ 07033 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 17期
关键词：
Nav1.7; Nav1.5; Pain; Sodium channel blockers; Pyrrolo-benzo-1,4-diazine; PAIN; GENES; EXPRESSION; NEURONS;
D O I：
10.1016/j.bmcl.2014.07.060
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of pyrrolo-benzo-1,4-diazine analogs have been synthesized and displayed potent Na(v)1.7 inhibitory activity and moderate selectivity over Na(v)1.5. The syntheses, structure-activity relationships, and selected pharmacokinetic data of these analogs are described. Compound 41 displayed anti-nociceptive efficacy in the rat CFA pain model at 100 mpk oral dosing. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4110 / 4113
页数：4
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