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

  • ACS Med Chem Lett. 2012 Aug 22;3(10):823-7. doi: 10.1021/ml300186g.
John M Keith  1 ,  Rich Apodaca  1 ,  Mark Tichenor  1 ,  Wei Xiao  1 ,  William Jones  1 ,  Joan Pierce  1 ,  Mark Seierstad  1 ,  James Palmer  1 ,  Michael Webb  1 ,  Mark Karbarz  1 ,  Brian Scott  1 ,  Sandy Wilson  1 ,  Lin Luo  1 ,  Michelle Wennerholm  1 ,  Leon Chang  1 ,  Sean Brown  1 ,  Michele Rizzolio  1 ,  Raymond Rynberg  1 ,  Sandra Chaplan  1 ,  J Guy Breitenbucher  1
Affiliations
  • 1. Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
PMID: 24900385 DOI: 10.1021/ml300186g
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.

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