• reversible inhibitors
• magl

Monoacylglycerol lipase (MAGL) is a serine hydrolase enzyme involved in many biological processes, such as the degradation of 2-arachidonoylglycerol (2-AG), one of the most important endocannabinoid neurotransmitters. Moreover, MAGL is upregulated in aggressive human cancer cells and primary tumors, where it has a unique role of providing lipolytic sources of free fatty acids for the synthesis of oncogenic signalling lipids that promote cancer aggressiveness.
Considering the numerous functions played by this enzyme, MAGL inhibitors may be useful for the treatment of pain, inflammation and cancer.
However, the use of irreversible MAGL inhibitors gives an unwanted chronic inactivation of this enzyme, which causes a functional antagonism of the endocannabinoid system, a mild physical dependence, and an impaired endocannabinoid-dependent synaptic plasticity. For all these reasons, the need to discover selective and reversible inhibitors is urgent. Considering what said above, the aim of this thesis work is the synthesis of reversible MAGL inhibitors.