| Title : Biaryl tetrazolyl ureas as inhibitors of endocannabinoid metabolism: modulation at the N-portion and distal phenyl ring - Ortar_2013_Eur.J.Med.Chem_63_118 |
| Author(s) : Ortar G , Morera E , De Petrocellis L , Ligresti A , Schiano Moriello A , Morera L , Nalli M , Ragno R , Pirolli A , Di Marzo V |
| Ref : Eur Journal of Medicinal Chemistry , 63 :118 , 2013 |
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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. |
| PubMedSearch : Ortar_2013_Eur.J.Med.Chem_63_118 |
| PubMedID: 23474898 |
Ortar G, Morera E, De Petrocellis L, Ligresti A, Schiano Moriello A, Morera L, Nalli M, Ragno R, Pirolli A, Di Marzo V (2013)
Biaryl tetrazolyl ureas as inhibitors of endocannabinoid metabolism: modulation at the N-portion and distal phenyl ring
Eur Journal of Medicinal Chemistry
63 :118
Ortar G, Morera E, De Petrocellis L, Ligresti A, Schiano Moriello A, Morera L, Nalli M, Ragno R, Pirolli A, Di Marzo V (2013)
Eur Journal of Medicinal Chemistry
63 :118