Abstract
1 alpha,2 beta(5Z),3 beta(1E,3S),4 alpha,5 alpha,6 alpha]-7-[5,6-Epoxy-3- (3-cyclohexyl-3-hydroxy-3-methyl-1-propenyl)-7-oxabicyclo[2.2.1]-hept-2- yl]-5-heptenoic acid (31) and [1 alpha,2 beta(5Z),3 beta(1E,3S),4 alpha,5 alpha,6 alpha]-7-[5,6-epoxy-3-[3-hydroxy-5-(p-hydroxyphenyl)-1- pentenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (37) were found to be selective TxA2 antagonists at the platelet and pulmonary thromboxane receptors. An efficient stereospecific synthesis of these compounds and a series of structural analogues is described. Compounds 31 and 37 both inhibited the bronchoconstriction induced by arachidonic acid in the anesthetized guinea pig.
MeSH terms
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Adenosine Diphosphate / antagonists & inhibitors
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Animals
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Arachidonic Acid
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Arachidonic Acids / antagonists & inhibitors
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Bridged Bicyclo Compounds / chemical synthesis*
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Bridged Bicyclo Compounds / pharmacology
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Bridged Bicyclo Compounds, Heterocyclic*
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Bridged-Ring Compounds / chemical synthesis*
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Chemical Phenomena
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Chemistry
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Epoxy Compounds / chemical synthesis
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Epoxy Compounds / pharmacology
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Fatty Acids, Monounsaturated / chemical synthesis*
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Fatty Acids, Monounsaturated / pharmacology
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Guinea Pigs
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Heptanes / chemical synthesis
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Heptanes / pharmacology
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Humans
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In Vitro Techniques
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Lung / drug effects
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Platelet Aggregation / drug effects
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Receptors, Prostaglandin / drug effects*
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Receptors, Thromboxane
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Structure-Activity Relationship
Substances
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Arachidonic Acids
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Bridged Bicyclo Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Bridged-Ring Compounds
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Epoxy Compounds
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Fatty Acids, Monounsaturated
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Heptanes
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Receptors, Prostaglandin
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Receptors, Thromboxane
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7-(5,6-epoxy-3-(3-hydroxy-5-(4-hydroxyphenyl)-1-pentenyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid
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7-(5,6-epoxy-3-(3-cyclohexyl-3-hydroxy-3-methyl-1-propenyl)-7-oxabicyclo(2.2.1)-hept-2-yl)-5-heptenoic acid
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Arachidonic Acid
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Adenosine Diphosphate