Discovery of boronic acids as novel and potent inhibitors of fatty acid amide hydrolase

Anna Minkkilä; Susanna M Saario; Heikki Käsnänen; Jukka Leppänen; Antti Poso; Tapio Nevalainen

doi:10.1021/jm801051t

Discovery of boronic acids as novel and potent inhibitors of fatty acid amide hydrolase

J Med Chem. 2008 Nov 27;51(22):7057-60. doi: 10.1021/jm801051t.

Authors

Anna Minkkilä¹, Susanna M Saario, Heikki Käsnänen, Jukka Leppänen, Antti Poso, Tapio Nevalainen

Affiliation

¹ Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. [email protected]

PMID: 18983140
DOI: 10.1021/jm801051t

Abstract

A series of commercial phenyl-, heteroaryl-, alkyl-, and alkenylboronic acids were evaluated for their FAAH and MGL inhibitory activities. The compounds were generally selective for FAAH, with IC50 in the nanomolar or low-micromolar range. Eight of these compounds inhibited MGL with IC50 in the micromolar range. The most potent compound, phenylboronic acid with para-nonyl substituent (13), inhibited FAAH and MGL with IC50 of 0.0091 and 7.9 microM, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases / antagonists & inhibitors*
Boronic Acids / chemical synthesis
Boronic Acids / chemistry
Boronic Acids / pharmacology*
Dose-Response Relationship, Drug
Drug Discovery*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Molecular Structure
Stereoisomerism
Structure-Activity Relationship

Substances

Boronic Acids
Enzyme Inhibitors
Amidohydrolases
fatty-acid amide hydrolase