Abstract
N-(3,5-Dichlorophenylsulfonyl)-(R)-thioprolyl biarylalanine 10a has been identified as a potent and specific antagonist of the alpha(4)beta(1) integrin. Altering the configuration of thioproline from R to S led to a series of dual antagonists of alpha(4)beta(1) and alpha(4)beta(7), and the N-acetyl analogue 8b was found to be the most potent dual antagonist. A binding site model for alpha(4)beta(1) and alpha(4)beta(7) is proposed to explain the structure-activity relationship.
MeSH terms
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Alanine / analogs & derivatives
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Alanine / chemistry
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Alanine / pharmacology*
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Integrin alpha4beta1
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Integrins / antagonists & inhibitors*
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Receptors, Lymphocyte Homing / antagonists & inhibitors*
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Structure-Activity Relationship
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / pharmacology*
Substances
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Integrin alpha4beta1
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Integrins
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N-(3,5-dichlorophenylsulfonyl)-thioprolyl biarylalanine
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Receptors, Lymphocyte Homing
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Sulfhydryl Compounds
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integrin alpha4beta7
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Alanine