Structural modifications of the cannabinoid side chain towards C3-aryl and 1',1'-cycloalkyl-1'-cyano cannabinoids

Demetris P Papahatjis; Victoria R Nahmias; Thanos Andreou; Pusheng Fan; Alexandros Makriyannis

doi:10.1016/j.bmcl.2005.12.026

Structural modifications of the cannabinoid side chain towards C3-aryl and 1',1'-cycloalkyl-1'-cyano cannabinoids

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1616-20. doi: 10.1016/j.bmcl.2005.12.026. Epub 2006 Jan 4.

Authors

Demetris P Papahatjis¹, Victoria R Nahmias, Thanos Andreou, Pusheng Fan, Alexandros Makriyannis

Affiliation

¹ Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vass. Constantinou, Athens 116-35, Greece. dpapah@eie.gr

PMID: 16387492
DOI: 10.1016/j.bmcl.2005.12.026

Abstract

The compounds reported in this study are Delta(8)-THC analogues in which the C3 five-carbon linear side chain of Delta(8)-THC was replaced with aryl and 1',1'-cycloalkyl substituents. Of the compounds described here analogues 2d (CB(1), K(i)=11.7 nM. CB(2), K(i)=9.39 nM) and 2f (CB(1), K(i)=8.26 nM. CB(2), K(i)=3.86 nM) exhibited enhanced binding affinities for CB(1) and CB(2), exceeding that of Delta(8)-THC. Efficient procedures for the synthesis of these novel cannabinoid analogues are described.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Dronabinol* / analogs & derivatives
Dronabinol* / chemical synthesis
Dronabinol* / pharmacology
Ligands
Mice
Prosencephalon / drug effects
Psychotropic Drugs* / chemical synthesis
Psychotropic Drugs* / chemistry
Psychotropic Drugs* / pharmacology
Radioligand Assay
Rats
Receptor, Cannabinoid, CB1 / metabolism*
Receptor, Cannabinoid, CB2 / metabolism*
Spleen / drug effects
Structure-Activity Relationship
Synaptosomes / drug effects

Substances

Ligands
Psychotropic Drugs
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2
Dronabinol