TY - JOUR
TI - The Application of 3D-QSAR Studies for Novel Cannabinoid Ligands Substituted at the C1΄ Position of the Alkyl Side Chain on the Structural Requirements for Binding to Cannabinoid Receptors CB1 and CB2
AU - Durdagi, A. Kapou, T. Kourouli, T. Andreou, S.P. Nikas, V.R. Nahmias, D. P. Papahatjis, M.G. Papadopoulos, T. Mavromoustakos
JO - Journal of Medicinal Chemistry
PY - 2007
VL - 50
TODO - 12
SP - 2875-2885
PB - American Chemical Society (ACS)
SN - 0022-2623, 1520-4804
TODO - 10.1021/jm0610705
TODO - 3D-QSAR,cannabinoid,receptors CB1
TODO - A set of 30 novel ∆8
-tetrahydrocannabinol and cannabidiol analogues were subjected to three-dimensional
quantitative structure-activity relationship studies using the comparative molecular field analysis (CoMFA)
and comparative molecular similarity indices analysis (CoMSIA) approaches. Using a combination of
molecular modeling techniques and NMR spectroscopy, the putative bioactive conformation of the most
potent cannabinoid (CB) ligand in the training set was determined. This conformer was used as the template
and CB1 and CB2 pharmacophore models were developed. These models were fitted with experimental
binding data and gave high correlation coefficients. Contour maps of the CB1 and CB2 models of CoMFA
and CoMSIA approaches show that steric effects dominantly determine the binding affinities. The CoMFA
and CoMSIA analyses based on the binding affinity data of CB ligands at the CB1 and CB2 receptors
allowed us to deduce the possible optimal binding positions. This information can be used for the design of
new CB analogues with enhanced activity and other tailored properties
ER -