Lipophilic amines as potent inhibitors of N-acylethanolamine-hydrolyzing acid amidase

  • Bioorg Med Chem. 2012 Jun 1;20(11):3658-65. doi: 10.1016/j.bmc.2012.03.065.
Yumiko Yamano  1 ,  Kazuhito Tsuboi ,  Yuki Hozaki ,  Kiyohiro Takahashi ,  Xing-Hua Jin ,  Natsuo Ueda ,  Akimori Wada
Affiliations
  • 1. Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada, Kobe 658-8558, Japan. [email protected]
PMID: 22542283 DOI: 10.1016/j.bmc.2012.03.065
Abstract

N-Acylethanolamines (NAEs) including N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine are endogenous lipid mediators. These molecules are degraded to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH) or NAE-hydrolyzing acid amidase (NAAA). Lipophilic amines, especially pentadecylamine (2c) and tridecyl 2-aminoacetate (11b), were found to exhibit potent NAAA inhibitory activities (IC(50)=5.7 and 11.8μM), with much weaker effects on FAAH. These simple structures would provide a scaffold for further improvement in NAAA inhibitory activity.

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