Send to

Choose Destination
J Med Chem. 2009 Apr 23;52(8):2506-14. doi: 10.1021/jm8016255.

New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo.

Author information

Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.


Bearing in mind the pharmacophoric requirements of both (-)-trans-Delta(9)-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 CB(2) ligand, with K(i) 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 CB(2) receptor (K(i)(CB(1)) = 1 muM, K(i)(CB(2)) = 35 nM).

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center