1210908-75-0Relevant academic research and scientific papers
Synthesis and evaluation of paracetamol esters as novel fatty acid amide hydrolase inhibitors
Onnis, Valentina,Congiu, Cenzo,Bj?rklund, Emmelie,Hempel, Franziska,S?derstr?m, Emma,Fowler, Christopher J.
supporting information; experimental part, p. 2286 - 2298 (2010/08/05)
Fatty acid amide hydrolase (FAAH) is the key hydrolytic enzyme for the endogenous cannabinoid receptor ligand anandamide. The synthesis and evaluation for their FAAH inhibitory activities of a series of 18 paracetamol esters are described. Structure-activity relationship studies indicated that the ester (33) with a 2-(4-(2-(trifluoromethyl)pyridin-4-ylamino)phenyl)acetic acid substituent was the most potent analogue in this series. The compound inhibited FAAH activity in a competitive manner with a Ki value of 0.16 μM. The compound was also able to inhibit the FAAH activity in rat basophilic leukemia cells as assessed by measuring either the hydrolysis of anandamide, the FAAH-dependent cellular accumulation of anandamide, or the FAAH-dependent recycling of tritium to the cell membranes. The compound also inhibited the activity of monoacylglycerol lipase (MGL), the enzyme responsible for the hydrolysis of the endogenous cannabinoid receptor ligand 2-arachidonoylglycerol, with an IC50 value of 1.9 μM. It is concluded that the compound may be a useful template for the design of potent novel inhibitors of FAAH.
