Channelpedia

PubMed 23474898


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1 , TRPV , TRPV1



Title: Biaryl tetrazolyl ureas as inhibitors of endocannabinoid metabolism: modulation at the N-portion and distal phenyl ring.

Authors: Giorgio Ortar, Enrico Morera, Luciano De Petrocellis, Alessia Ligresti, Aniello Schiano Moriello, Ludovica Morera, Marianna Nalli, Rino Ragno, Adele Pirolli, Vincenzo Di Marzo

Journal, date & volume: Eur J Med Chem, 2013 May , 63, 118-32

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23474898


Abstract
In the present study, we have further extended the structure-activity relationships for the tetrazolyl ureas class of compounds as potential FAAH and/or MAGL inhibitors, by replacing the dimethylamino group of the parent compounds 1 and 2 with bulkier groups or by introducing on the distal phenyl ring of 1 and 2 a selected set of substituents. Some of the new compounds (16, 20, 21, 25, and 28) inhibited FAAH potently (IC50 = 3.0-9.7 nM) and selectively (39- to more than 141-fold) over MAGL, while tetrazole 27 turned out to be a promising dual FAAH-MAGL inhibitor of potential therapeutic use. Covalent docking studies on FAAH indicated that the binding modes of tetrazoles 1-32 did not display a unique pattern. The ability of tetrazoles 1-32 to act as TRPV1 and TRPA1 modulators was also investigated.