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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. June 2002, Volume 1, Number 6, 300-309 |
Quantitative-Structure Activity Relationships on Thromboxane Receptor
Antagonists
Dimitra Hadjipavlou-Litina and Christos A. Kontogiorgis
Internet Electron. J. Mol. Des. 2002, 1, 300-309
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Abstract:
TXA2 is an unstable metabolite of arachidonic acid and a potent
inducer of platelet aggregation, vasoconstriction and
bronchoconstriction. TXA2 receptor antagonists are effective for the
treatment of circulatory disorders, angina and stroke. Some heptenoic
acids synthesized as novel TXA2 receptor antagonists were collected
from the literature. For them, quantitative structure-activity
relationships study were determined in order to provide a simple
description of the physicochemical parameters which are involved in
the (±)-(5Z)-7-[3-endo-[(phenylsulfonyl)amino]bicyclo[2.2.1]hept-2-
exo-yl]heptenoic acids TXA2 receptor site of action. The analysis was
done by using the C-QSAR suite of programs (Biobyte). The
evaluation of the quantitative structure-activity relationships (QSAR)
revealed that the primary physicochemical feature influencing the in vitro
TXA2 receptor antagonists is the overall molar refractivity
(CMR) of the molecule. The Swain-Lupton factor F was found to be
also significant. A significant parabolic correlation was observed
between the CMR of the studied compounds and the in vitro inhibition
of the aggregation of washed platelets. The QSAR study also
demonstrated that the inhibitory activity is affected by the Sterimol
minimum width B1.
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