| Title : The discovery of azetidine-piperazine di-amides as potent, selective and reversible monoacylglycerol lipase (MAGL) inhibitors - Zhu_2020_Bioorg.Med.Chem.Lett_30_127243 |
| Author(s) : Zhu B , Connolly PJ , Zhang YM , McDonnell ME , Bian H , Lin SC , Liu L , Zhang SP , Chevalier KM , Brandt MR , Milligan CM , Flores CM , Macielag MJ |
| Ref : Bioorganic & Medicinal Chemistry Lett , 30 :127243 , 2020 |
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Abstract :
Monoacylglycerol lipase (MAGL) is the enzyme that is primarily responsible for hydrolyzing the endocannabinoid 2-arachidononylglycerol (2-AG) to arachidonic acid (AA). It has emerged in recent years as a potential drug target for a number of diseases. Herein, we report the discovery of compound 6g from a series of azetidine-piperazine di-amide compounds as a potent, selective, and reversible inhibitor of MAGL. Oral administration of compound 6g increased 2-AG levels in rat brain and produced full efficacy in the rat complete Freund's adjuvant (CFA) model of inflammatory pain. |
| PubMedSearch : Zhu_2020_Bioorg.Med.Chem.Lett_30_127243 |
| PubMedID: 32527545 |
| Gene_locus related to this paper: human-MGLL |
| Gene_locus | human-MGLL |
Zhu B, Connolly PJ, Zhang YM, McDonnell ME, Bian H, Lin SC, Liu L, Zhang SP, Chevalier KM, Brandt MR, Milligan CM, Flores CM, Macielag MJ (2020)
The discovery of azetidine-piperazine di-amides as potent, selective and reversible monoacylglycerol lipase (MAGL) inhibitors
Bioorganic & Medicinal Chemistry Lett
30 :127243
Zhu B, Connolly PJ, Zhang YM, McDonnell ME, Bian H, Lin SC, Liu L, Zhang SP, Chevalier KM, Brandt MR, Milligan CM, Flores CM, Macielag MJ (2020)
Bioorganic & Medicinal Chemistry Lett
30 :127243