Aryl Piperazinyl Ureas as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) in Rat, Dog, and Primate

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• 作者：John M. Keith ; Rich Apodaca ; Mark Tichenor ; Wei Xiao ; William Jones ; Joan Pierce ; Mark Seierstad ; James Palmer ; Michael Webb ; Mark Karbarz ; Brian Scott ; Sandy Wilson ; Lin Luo ; Michelle Wennerholm ; Leon Chang ; Sean Brown ; Michele Rizzolio ; Raymond Rynberg ; Sandra Chaplan ; J. Guy Breitenbucher
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：October 11, 2012
• 年：2012
• 卷：3
• 期：10
• 页码：823-827
• 全文大小：248K
• 年卷期：v.3,no.10(October 11, 2012)
• ISSN：1948-5875

文摘

A series of aryl piperazinyl ureas that act as covalent inhibitors of fatty acid amide hydrolase (FAAH) is described. A potent and selective (does not inhibit FAAH-2) member of this class, JNJ-40355003, was found to elevate the plasma levels of three fatty acid amides: anandamide, oleoyl ethanolamide, and palmitoyl ethanolamide, in the rat, dog, and cynomolgous monkey. The elevation of the levels of these lipids in the plasma of monkeys suggests that FAAH-2 may not play a significant role in regulating plasma levels of fatty acid ethanolamides in primates.

Keywords:

FAAH; urea; ethanolamides; FAAH-2; enzyme; anandamide