Abstract
6-[4-Amidinobenzoyl]amino]-tetralone-2-acetic acid is a potent antagonist of GPIIb-IIIa. Substitution in the meta position of the benzamidine, or replacement with a heteroaryl amidine was tolerated in this series. Use of an acyl-linked 4-alkyl piperidine as an arginine isostere also provided active compounds. Compounds from this series provided substantial systemic exposure in the rat following oral administration.
MeSH terms
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Acetates / metabolism*
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Adenosine Diphosphate / pharmacology
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Amidines / metabolism*
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Animals
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Arginine / chemistry
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Benzamidines / chemistry
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Biological Availability
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Drug Evaluation
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Enzyme-Linked Immunosorbent Assay
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Fibrinogen / metabolism
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Humans
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Inhibitory Concentration 50
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Models, Molecular
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Platelet Aggregation / drug effects
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Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
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Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
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Prodrugs / chemical synthesis
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Prodrugs / chemistry
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Prodrugs / pharmacokinetics
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Protein Binding / drug effects
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Protein Structure, Secondary
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Rats
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Stereoisomerism
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Tetralones*
Substances
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6-((4-amidinobenzoyl)amino)tetralone-2-acetic acid
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Acetates
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Amidines
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Benzamidines
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Platelet Glycoprotein GPIIb-IIIa Complex
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Prodrugs
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Tetralones
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Adenosine Diphosphate
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Fibrinogen
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Arginine
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benzamidine