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

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

Affiliation

  • 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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