Novel Analogues of Arachidonylethanolamide (Anandamide): Affinities for the CB1 and CB2 Cannabinoid Receptors and Metabolic Stability

摘要: Several analogues of the endogenous cannabinoid receptor ligand arachidonylethanolamide (anandamide) were synthesized and evaluated in order to study (a) structural requirements for high-affinity binding CB1 CB2 receptors (b) their hydrolytic stability toward anandamide amidase. The series reported here was aimed at exploring structure−activity relationships (SAR) primarily with regard stereoelectronic ethanolamido headgroup interaction active site. Receptor affinities, as Ki values, obtained by a standard assay using [3H]CP-55,940 radioligand, while amidase comparing each analogue presence absence phenylmethanesulfonyl fluoride (PMSF), serine protease blocker inhibitor Introduction methyl group 1‘- 2‘-positions or substitution butylamido group...