1-Aryl-2-((6-aryl)pyrimidin-4-yl)amino)ethanols as competitive inhibitors of fatty acid amide hydrolase

  • Bioorg Med Chem Lett. 2014 Mar 1;24(5):1280-4. doi: 10.1016/j.bmcl.2014.01.064.
John M Keith  1 ,  Natalie Hawryluk  2 ,  Richard L Apodaca  2 ,  Allison Chambers  2 ,  Joan M Pierce  2 ,  Mark Seierstad  2 ,  James A Palmer  2 ,  Michael Webb  2 ,  Mark J Karbarz  2 ,  Brian P Scott  2 ,  Sandy J Wilson  2 ,  Lin Luo  2 ,  Michelle L Wennerholm  2 ,  Leon Chang  2 ,  Michele Rizzolio  2 ,  Sandra R Chaplan  2 ,  J Guy Breitenbucher  2
Affiliations
  • 1. Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States. Electronic address: [email protected].
  • 2. Janssen Pharmaceutical Companies of Johnson & Johnson, 3210 Merryfield Row, San Diego, CA 92121, United States.
PMID: 24513048 DOI: 10.1016/j.bmcl.2014.01.064
Abstract

A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.

Keywords
Analgesia; Crystal structure; Endo-cannabinoids; Enzymes; Fatty acid amide hydrolase (FAAH).
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