1150586-63-2Relevant academic research and scientific papers
New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo
Brizzi, Antonella,Brizzi, Vittorio,Cascio, Maria Grazia,Corelli, Federico,Guida, Francesca,Ligresti, Alessia,Maione, Sabatino,Martinelli, Adriano,Pasquini, Serena,Tuccinardi, Tiziano,Di Marzo, Vincenzo
supporting information; experimental part, p. 2506 - 2514 (2010/03/26)
Bearing in mind the pharmacophoric requirements of both (-)-trans-Δ9-tetrahydrocannabinol (THC) and anandamide (AEA), we designed a novel pharmacophore consisting of both a rigid aromatic backbone and a flexible chain with the aim to develop a series of stable and potent ligands of cannabinoid receptors. In this paper we report the synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide "hybrids" differing in the side chain group. Compounds bearing a 2-methyloctan-2-yl group at position 5 showed a significantly higher affinity for cannabinoid (CB) receptors, in particular when an alkyloxy chain of 7 or 10 carbon atoms was also present at position 1. Derivative 32 was a potent CB 1 and CB2 ligand, with Ki values similar to that of WIN 55-212 and potent antinociceptive activity in vivo. Moreover, derivative 38, although less potent, proved to be the most selective ligand for CB2 receptor (Ki(CB1)) 1 μM, K i(CB2)) 35 nM).
