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

ABSTRACT: 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.

SUBMITTER: Keith JM

PROVIDER: S-EPMC4025847 | biostudies-other | 2012 Oct

REPOSITORIES: biostudies-other

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

Keith John M JM Apodaca Rich R Tichenor Mark M Xiao Wei W Jones William W Pierce Joan J Seierstad Mark M Palmer James J Webb Michael M Karbarz Mark M Scott Brian B Wilson Sandy S Luo Lin L Wennerholm Michelle M Chang Leon L Brown Sean S Rizzolio Michele M Rynberg Raymond R Chaplan Sandra S Breitenbucher J Guy JG

ACS medicinal chemistry letters 20120822 10

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 reg ...[more]

PMID: 24900385

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