Abstract
In the course of our research for the low-molecular weight RGD peptide mimics, we have found that a rigid 2-acylimino-3H-thiazoline structure is suitable for the peptide backbone mimics. Introduction of amidinophenyl and beta-alanine moiety as arginine and aspartic acid side-chain surrogates to this backbone mimic resulted in a highly potent fibrinogen receptor antagonist 2-(4-amidinobenzoylimino)-3,4-dimethyl-N-(2-carboxyethyl)-3H-thiazoline-5-carboxamide (7c), namely PS-028 (Ki = 46.5 +/- 5.8 microM).
MeSH terms
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Animals
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Binding Sites / physiology
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Blood Platelets / metabolism*
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Cell Adhesion / drug effects
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Dogs
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Enzyme-Linked Immunosorbent Assay
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Fibrinogen / metabolism*
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Guinea Pigs
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Humans
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Inhibitory Concentration 50
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Intercellular Signaling Peptides and Proteins
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Mice
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Oligopeptides / chemical synthesis
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Peptides / pharmacology
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Platelet Aggregation Inhibitors / chemical synthesis
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Platelet Aggregation Inhibitors / metabolism
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Platelet Aggregation Inhibitors / pharmacology*
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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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Thiazoles / chemical synthesis
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Thiazoles / metabolism
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Thiazoles / pharmacology*
Substances
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2-acylimino-3H-thiazoline
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Intercellular Signaling Peptides and Proteins
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Oligopeptides
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Peptides
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Platelet Aggregation Inhibitors
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Platelet Glycoprotein GPIIb-IIIa Complex
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Thiazoles
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echistatin
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arginyl-glycyl-aspartic acid
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Fibrinogen