Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 22, Pages 10074-10089Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm301205j
Keywords
-
Categories
Funding
- National Institute on Drug Abuse [DA009158, DA003801, DA007215]
Ask authors/readers for more resources
Sulfonyl fluorides are known to inhibit esterases. Early work, from our laboratory has identified hexadecyl sulfonylfluoride (AM374) as a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase (FAAH). We now report on later generation sulfonyl fluoride analogs that exhibit potent and selective inhibition of FAAH. Using recombinant rat and human FAAH, we show that 5-(4-hydroxyphenyl)pentanesulfonyl fluoride (AM3506) has similar inhibitory activity for both the rat and the human enzyme, while dilution assays and mass spectrometry analysis suggest that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner. Our SAR results are highlighted by molecular docking of key analogs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available