Premium
Electrostatic interactions and conformation of some thromboxane antagonists
Author(s) -
Wilkinson A. J.,
Warwick C. M.,
Davies R. H.
Publication year - 1988
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560340708
Subject(s) - moiety , chemistry , pyranose , stereochemistry , conformational isomerism , ring (chemistry) , side chain , prostaglandin h2 , thromboxane a2 , receptor , organic chemistry , biochemistry , molecule , polymer
A class of thromboxane antagonists exists where the prostaglandin side chain containing the C 16 hydroxyl moiety is replaced by a phenyl ring, and the bridged six‐membered pyranose moiety by cyclohexane, pyranose and dioxane ring systems. Analysis of antagonist potency data in terms of a binding constant model previously used for membrane bound receptor–drug interactions shows that the major patterns of antagonist potency are governed as much by axial/equatorial conformer preference of the phenyl moiety and its orientation as by electrostatic effects of the aliphatic ring oxygen atoms. The conformational restriction of the two substituted side chains of the σ‐bonded 6‐membered ring is shown to be a primary requirement for binding to thromboxane receptors, and a quantitative separation of electrostatic and conformational components in the potency data is attempted.