2. Academic Validation
  3. Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors

Synthesis, SAR study, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase (FAAH) inhibitors

  • Bioorg Med Chem. 2013 Jan 1;21(1):28-41. doi: 10.1016/j.bmc.2012.11.006.
Mitsunori Kono 1,  Takahiro Matsumoto,  Toru Kawamura,  Atsushi Nishimura,  Yoshihiro Kiyota,  Hideyuki Oki,  Junichi Miyazaki,  Shigeru Igaki,  Craig A Behnke,  Masato Shimojo,  Masakuni Kori
Affiliations

Affiliation

  • 1 Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. mitsunori.kouno@takeda.com
PMID: 23218778 DOI: 10.1016/j.bmc.2012.11.006
Abstract

A series of piperazine ureas was designed, synthesized, and evaluated for their potential as novel orally available fatty acid amide hydrolase (FAAH) inhibitors that are therapeutically effective against pain. We carried out an optimization study of the lead compound 3 to improve its DMPK profile as well as in vitro potency. We identified the thiazole compound 60j with potent inhibitory activity, high brain permeability, and good bioavailability. Compound 60j showed a potent and dose-dependent anti-nociceptive effect in the acetic acid-induced writhing test in mice.

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