Computer-Assisted Determination of Minimum Energy Conformations. 7. A pharmacophore Model of the Active Region of the Alpha2-Adrenoceptor.

Molecular modeling and computational chemistry techniques are used to analyze compounds in developing pharmacophores of biological receptors to use as templates in structure activity relationship studies and to design new chemicals having physiological activity of interest. In this study, the results of x-ray crystal analyses and PM3 semi-empirical molecular orbital conformational analyses are used to determine the three-dimensional representations of selected adrenergic compounds known to be agonists with the alpha2-adrenoceptor in achieving optimized geometries and electrostatic parameters. The alpha2- adrenergic agonists interact with the adrenergic system receptors to produce various increases or decreases in hemodynamic responses (i.e., hypertension, hypotension, bradycardia) and sedation. A pharmacophore model of the active region-of the alpha2-adrenoceptor is described based on the superimposition of common structural, electrostatic, and physicochemical features of the compounds. Using the model to predict compound adrenergic activity and to design alpha2- adrenergic compounds is discussed.... Molecular modeling, Clonidine, Pharmacophore, Theoretical chemistry, Alpha2-adrenergic compounds.