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Abstract: The regulation of 2-arachidonoylglycerol (2-AG) levels is a major issue as 2-AG has been proven to participate in numerous physiopathological phenomena such as neuroprotection or analgesia. Octhilinone, a cysteine-reagent compound, has recently been shown to inhibit in the nanomolar range monoacylglycerol lipase (MAGL), the major enzyme responsible for the degradation of 2-AG. Here, we further investigate the mechanism by which octhilinone and its benzisothiazolinone analog inhibit human MAGL. We also provide new information on the structural requirements for MAGL inhibition by these compounds. Finally, we describe for N-octylbenzisothiazolinone a mode of inhibition which is partially different from that described for octhilinone, especially with regard to the targeted cysteine residues in the vicinity of the catalytic site. [Copyright &y& Elsevier]

Graphical abstract The present study describes the optimization of a new method of synthesis of highly functionalized 5-bromo-2-amino-1,3-thiazoles by a rapid and efficient one-pot method, using simple starting materials and mild conditions. Interestingly some of the synthesized compounds demonstrate promising monoacylglycerol lipase inhibition properties. Highlights • Convenient one-pot synthesis of highly functionalized 5-bromo-2-amino-1,3-thiazoles. • Potential MAGL inhibitors. • Safe and efficient bromination reaction. Abstract Highly functionalized 5-bromo-2-amino-1,3-thiazoles bearing various substituents could be easily prepared by a rapid and efficient one-pot method, using simple starting materials and mild conditions while avoiding the use of metal catalysts or inconvenient reagents such as elemental halogens. These useful products can serve as starting materials for other reactions or as pharmacologically interesting compounds. In our work we have shown that the resulting 5-bromothiazole compounds could lead to monoacylglycerol lipase (MAGL) inhibition in the μM range. [ABSTRACT FROM AUTHOR]