The discovery of azetidine-piperazine di-amides as potent, selective and reversible monoacylglycerol lipase (MAGL) inhibitors.
Basic Information
ID: ALA4622904
Journal: Bioorg Med Chem Lett
Title: The discovery of azetidine-piperazine di-amides as potent, selective and reversible monoacylglycerol lipase (MAGL) inhibitors.
Authors: 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.
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.
CiteXplore: 32527545
DOI: 10.1016/j.bmcl.2020.127243
Patent ID: ┄