Detail of "149301-79-1"

Reference

Fatty acid sulfonyl fluorides inhibit anandamide metabolism and bind to the cannabinoid receptor

Fatty acid sulfonyl fluorides inhibit anandamide metabolism and bind to the cannabinoid receptor. Deutsch, D. G.; Lin, S.; Hill, W. A. G.; Morse, K. L.; Salehani, D.; Arreaza, G.; Omeir, R. L.; Makriyannis, A. (Dep. Biochem. Cell Biol., State Univ. New York, Stony Brook, NY 11794, USA). Biochemical and Biophysical Research Communications, 231(1), 217-221 (English) 1997 Academic.Several substances with their cas registry numbers 157482-38-7 and 149301-79-1 may be metioned in this study. CODEN: BBRCA9. ISSN: 0006-291X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 13 Arachidonoyl ethanolamide (anandamide) is an endogenous ligand for cannabinoid receptors (CB1, CB2) and a putative neurotransmitter. Phenylmethylsulfonyl fluoride (PMSF) is an inhibitor of the enzyme (an amidase) which hydrolyzes anandamide to arachidonic acid and ethanolamine. The authors report here that fatty acid sulfonyl fluorides are potent inhibitors of anandamide metab. To investigate the SAR of these anandamide amidase inhibitors, the authors tested a series of fatty acid (C12 to C20) sulfonyl fluorides both as inhibitors of anandamide degrdn. and as ligands for the central cannabinoid receptor (CB1). AM374 (palmitylsulfonyl fluoride, C16) was approx. 20 times more potent than PMSF and 50 times more potent than arachidonyltrifluoromethyl ketone in preventing the hydrolysis of anandamide in brain homogenates. AM374 was over a thousand-fold more effective than PMSF in inhibiting the amidase in cultured cells. The C12 to C18 sulfonyl fluoride analogs were equipotent as inhibitors of the amidase and the reverse reaction (the synthase) with nanomolar IC50 values. These compds. generally showed decreasing affinity for the CB1 receptor as the chain length increased; thus, C12 sulfonylfuoride had an IC50 of 18 nM and C20 sulfonylfuoride had an IC50 of 78 mM. The C14, C16, and C18 sulfonyl fluorides showed high selectivity for the amidase over the CB1 receptor and thus are potentially useful selective anandamide amidase inhibitors. .