2-D and 3-D modeling of imidazoline receptor ligands: insights into pharmacophore.
A 3-D quantitative structure-activity relationship (3-D QSAR) study was carried out using comparative molecular field analysis (CoMFA) on both imidazoline (I2R) and alpha 2 receptor binding affinities of a large series of 2-substituted imidazolines. Significant cross-validated correlations, having promising predictive ability, were obtained along with 3-D pharmacophore models that defined the spatial regions where steric and electrostatic interactions may modulate the in vitro binding affinities and indicated possible physicochemical and structural requirements for I2/alpha 2 receptor selectivity.
Carrieri
A
A
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Italy.
Brasili
L
L
Leonetti
F
F
Pigini
M
M
Giannella
M
M
Bousquet
P
P
Carotti
A
A
D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D054755:Imidazoline Receptors; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011955:Receptors, Drug / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug