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Bioorg Med Chem. 2010 Dec 15;18(24):8463-77. doi: 10.1016/j.bmc.2010.10.050. Epub 2010 Oct 27.

Synthesis, binding studies and molecular modeling of novel cannabinoid receptor ligands.

Author information

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Al Tagamoa Al Khames, New Cairo City 11835, Egypt.

Abstract

In the present work, we report upon the design, synthesis and biological evaluation of new anandamide derivatives obtained by modifications of the fatty acyl chain and/or of the ethanolamide 'tail'. The compounds are of the general formula: 6-(substituted-phenyl)/naphthyl-4-oxohex-5-enoic acid N-substituted amide and 7-naphthyl-5-oxohept-6-enoicacid N-substituted amide. The novel compounds had been evaluated for their binding affinity to CB1/CB2 cannabinoid receptors, binding studies showed that some of the newly developed compounds have measurable affinity and selectivity for the CB2 receptor. Compounds XI and XVIII showed the highest binding affinity for CB2 receptor. None of the compounds exhibited inhibitory activity towards anandamide hydrolysis, thus arguing in favor of their enzymatic stability. The structure-activity relationship has been extensively studied through a tailor-made homological model using constrained docking in addition to pharmacophore analysis, both feature and field based.

PMID:
21074998
DOI:
10.1016/j.bmc.2010.10.050
[Indexed for MEDLINE]

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