| Title : Discovery of 1,5-Diphenylpyrazole-3-Carboxamide Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase (MAGL) Inhibitors - Aghazadeh Tabrizi_2018_J.Med.Chem_61_1340 |
| Author(s) : Aghazadeh Tabrizi M , Baraldi PG , Baraldi S , Ruggiero E , De Stefano L , Rizzolio F , Di Cesare Mannelli L , Ghelardini C , Chicca A , Lapillo M , Gertsch J , Manera C , Macchia M , Martinelli A , Granchi C , Minutolo F , Tuccinardi T |
| Ref : Journal of Medicinal Chemistry , 61 :1340 , 2018 |
| Abstract : Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays an important role in the degradation of the endocannabinoid neurotransmitter 2-arachidonoylglycerol, which is implicated in many physiological processes. Beyond the possible utilization of MAGL inhibitors as anti-inflammatory, antinociceptive, and anticancer agents, their application has encountered obstacles due to the unwanted effects caused by the irreversible inhibition of this enzyme. The possible application of reversible MAGL inhibitors has only recently been explored, mainly due to the deficiency of known compounds possessing efficient reversible inhibitory activities. In this work, we report a new series of reversible MAGL inhibitors. Among them, compound 26 showed to be a potent MAGL inhibitor (IC50 = 0.51 muM, Ki = 412 nM) with a good selectivity versus fatty acid amide hydrolase (FAAH), alpha/beta-hydrolase domain-containing 6 (ABHD6), and 12 (ABHD12). Interestingly, this compound also possesses antiproliferative activities against two different cancer cell lines and relieves the neuropathic hypersensitivity induced in vivo by oxaliplatin. |
| ESTHER : Aghazadeh Tabrizi_2018_J.Med.Chem_61_1340 |
| PubMedSearch : Aghazadeh Tabrizi_2018_J.Med.Chem_61_1340 |
| PubMedID: 29309142 |
Aghazadeh Tabrizi M, Baraldi PG, Baraldi S, Ruggiero E, De Stefano L, Rizzolio F, Di Cesare Mannelli L, Ghelardini C, Chicca A, Lapillo M, Gertsch J, Manera C, Macchia M, Martinelli A, Granchi C, Minutolo F, Tuccinardi T (2018)
Discovery of 1,5-Diphenylpyrazole-3-Carboxamide Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase (MAGL) Inhibitors
Journal of Medicinal Chemistry
61 :1340
Aghazadeh Tabrizi M, Baraldi PG, Baraldi S, Ruggiero E, De Stefano L, Rizzolio F, Di Cesare Mannelli L, Ghelardini C, Chicca A, Lapillo M, Gertsch J, Manera C, Macchia M, Martinelli A, Granchi C, Minutolo F, Tuccinardi T (2018)
Journal of Medicinal Chemistry
61 :1340