Abstract
A series of ring constrained analogues of the GPIIb/IIIa receptor antagonist XR299 (1) was investigated as potential inhibitors of glycoprotein IIb/IIIa, a platelet receptor that plays a key role in platelet aggregation and platelet adhesion. Ring size was found to have a large effect on in vitro potency. Selected compounds showed good in vitro activity, a preference for binding to activated platelets, and modest duration of action when dosed i.v. as a racemate in a canine model.
MeSH terms
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Humans
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In Vitro Techniques
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Molecular Conformation
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Nitrogen / chemistry
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Platelet Adhesiveness / drug effects
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Platelet Aggregation / drug effects
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Platelet Aggregation Inhibitors / chemical synthesis
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Platelet Aggregation Inhibitors / pharmacology
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Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
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beta-Alanine / chemistry*
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beta-Alanine / pharmacology*
Substances
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Isoxazoles
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Platelet Aggregation Inhibitors
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Platelet Glycoprotein GPIIb-IIIa Complex
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XR 299
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beta-Alanine
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Nitrogen