title: 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.
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Keith
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Rich
authors.initials: R
authors.lastname: Apodaca
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Tichenor
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: William
authors.initials: W
authors.lastname: Jones
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Joan
authors.initials: J
authors.lastname: Pierce
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Seierstad
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: James
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Webb
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Karbarz
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Scott
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Sandy
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Luo
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Wennerholm
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Leon
authors.initials: L
authors.lastname: Chang
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Sean
authors.initials: S
authors.lastname: Brown
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michele
authors.initials: M
authors.lastname: Rizzolio
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Rynberg
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Chaplan
authors.affiliation: Janssen Pharmaceutical Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: J Guy
authors.initials: JG
authors.lastname: Breitenbucher
keywords: FAAH; FAAH-2; anandamide; enzyme; ethanolamides; urea