ISSN:
0020-7608
Keywords:
Computational Chemistry and Molecular Modeling
;
Atomic, Molecular and Optical Physics
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Leukotrienes and thromboxane A 2 are autacoids derived from arachidonic acid (5, 8, 11, 14-icosatretraenoic acid). They are synthesized in cells by 5-lipoxygenase and thromboxane synthase, respectively. Leukotrienes are related to inflammatory and allergic diseases, while thromboxane A2 is a potent platelet aggregating and vasoconstrictor agent involved in cardiovascular pathologies. In this article we have calculated partial potential energy surfaces at the AM1 level for some 5-lipoxygenase inhibitors, thromboxane synthase inhibitors, thromboxane A2 receptor antagonists, and a dual blocker which inhibits thromboxane synthase and antagonizes thromboxane A2 receptor. Our objective was to identify stereoelectronic properties and topographical requirements for these compounds that could be related to their biological activities. Based on our results and on molecular mechanisms of pharmacological action, we were able to propose new potential 5-lipoxygenase inhibitors and dual blockers derived from pyrazole, pyrrole, 1, 2, 3-triazole, and 1, 2, 4-triazole. © 1995 John Wiley & Sons, Inc.
Additional Material:
8 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/qua.560560719
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