Abstract
The use of 5,6-bicyclic amidines as arginine surrogates in the design of a novel class of potent platelet glycoprotein IIb-IIIa receptor (GPIIb-IIIa) antagonists is described. The additional conformational restriction offered by the bicyclic nucleus results in 20-400-fold increases in potency compared to the freely flexible, acyclic benzamidine counterpart. The design, synthesis, structure-activity relationships (SAR), and in vitro activity of this novel class of GPIIb-IIIa antagonists are presented.
MeSH terms
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Arginine*
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Benzamidines / chemical synthesis*
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Benzamidines / chemistry
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Benzamidines / pharmacology*
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Enzyme-Linked Immunosorbent Assay
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Fibrinogen / metabolism
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Humans
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Indicators and Reagents
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Models, Molecular
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Molecular Conformation
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Molecular Structure
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Platelet Aggregation / drug effects
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Platelet Aggregation Inhibitors / chemical synthesis*
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Platelet Aggregation Inhibitors / chemistry
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Platelet Aggregation Inhibitors / pharmacology
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Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Benzamidines
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Indicators and Reagents
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Platelet Aggregation Inhibitors
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Platelet Glycoprotein GPIIb-IIIa Complex
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Fibrinogen
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Arginine