Computer-Assisted Determination of Minimum Energy Conformations. Vol 8. Structure Cardiovascular Activity of Detomidine Analogues.
Abstract
A series of detomidine-like arylalkyl imidazoles and compounds known to be agonists at the alpha 2 adrenergic receptor are studied to identify structural, electrostatic, and physicochemical parameters related to various cardiovascular (tachycardia, hypotension, bradycardia, mean arterial pressure) activities. Semi-empirical PM3 quantum chemical calculations determined the lowest energy conformations and electrostatic parameters of each compound. A molecular modeling analysis for compound/proposed adrenoceptor pharmacophore interaction provided additional features for analysis. Multiple regression analysis correlated each compound's octanol/water partition coefficient; the electrostatic environment around a specific nitrogen region of the module, geometric positions of compound functional groups in relationship to a proposed binding site on the adrenoceptor pharmacophore; and the presence of specific compound functional groups with cardiovascular activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1993
- Accession Number
- ADA263901
Entities
People
- Brian S. Meehan
- William P. Ashman
Organizations
- Edgewood Chemical Biological Center