Abstract
Mimetics of the RGD tripeptide are described that are potent, selective antagonists of the integrin receptor, alpha(v)beta(3). The use of the 5,6,7,8-tetrahydro[1,8]naphthyridine group as a potency-enhancing N-terminus is demonstrated. Two 3-substituted-3-amino-propionic acids previously contained in alpha(IIb)beta(3) antagonists were utilized to enhance binding affinity and functional activity for the targeted receptor. Further affinity increases were then achieved through the use of cyclic glycyl amide bond constraints.
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry
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Amides / pharmacology
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Binding, Competitive
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Drug Design
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Drug Evaluation, Preclinical
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Humans
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Inhibitory Concentration 50
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Molecular Conformation
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Molecular Mimicry
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Osteoporosis / prevention & control
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Platelet Aggregation / drug effects
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Receptors, Vitronectin / antagonists & inhibitors*
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Receptors, Vitronectin / metabolism
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Structure-Activity Relationship
Substances
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Amides
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Oligopeptides
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Receptors, Vitronectin
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arginyl-glycyl-aspartic acid