Heteroarylureas with spirocyclic diamine cores as inhibitors of fatty acid amide hydrolase

被引：19

作者：

Keith, John M. ^{[1
]}

Jones, William M. ^{[1
]}

Pierce, Joan M. ^{[1
]}

Seierstad, Mark ^{[1
]}

Palmer, James A. ^{[1
]}

Webb, Michael ^{[1
]}

Karbarz, Mark J. ^{[1
]}

Scott, Brian P. ^{[1
]}

Wilson, Sandy J. ^{[1
]}

Luo, Lin ^{[1
]}

Wennerholm, Michelle L. ^{[1
]}

Chang, Leon ^{[1
]}

Brown, Sean M. ^{[1
]}

Rizzolio, Michele ^{[1
]}

Rynberg, Raymond ^{[1
]}

Chaplan, Sandra R. ^{[1
]}

Breitenbucher, J. Guy ^{[1
]}

机构：

[1] Janssen Res & Dev LLC, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 03期

关键词：

FAAH; Hydrolase; Covalent inhibitor; Spirocycles; ALPHA-KETOHETEROCYCLE INHIBITORS; DISCOVERY; POTENT; RECEPTOR; FAAH; PAIN; PALMITOYLETHANOLAMIDE; PF-04457845; ANANDAMIDE; BINDING;

D O I：

10.1016/j.bmcl.2013.12.113

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of mechanism based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with spirocyclic diamine cores is described. A potent member of this class, (37), was found to inhibit FAAH centrally, elevate the brain levels of three fatty acid ethanolamides [FAAs: anandamide (AEA), oleoyl ethanolamide (OEA) and palmitoyl ethanolamide (PEA)], and was moderately efficacious in a rat model of neuropathic pain. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：737 / 741

页数：5

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