Abstract
Solid-phase synthesis and SAR of integrin alpha(V)beta3-receptor antagonists containing a urea moiety as non-basic guanidine mimetic are described. The most potent compounds exhibited IC(50) values towards alpha(V)beta3 in the nanomolar range and high selectivity versus related integrins like alpha(IIb)beta3. For selected examples efficacy in functional cellular assays is demonstrated.
MeSH terms
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Animals
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CHO Cells
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Cell Adhesion / drug effects*
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Cricetinae
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Drug Design
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Humans
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Models, Molecular
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Molecular Conformation
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Receptors, Vitronectin / antagonists & inhibitors*
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Structure-Activity Relationship
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Urea / analogs & derivatives*
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Urea / chemical synthesis*
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Urea / pharmacology
Substances
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Receptors, Vitronectin
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Urea