Abstract
A study of the S1 binding of lead 5-methylthiothiophene amidine 3, an inhibitor of urokinase-type plasminogen activator, was undertaken by the introduction of a variety of substituents at the thiophene 5-position. The 5-alkyl substituted and unsubstituted thiophenes were prepared using organolithium chemistry. Heteroatom substituents were introduced at the 5-position using a novel displacement reaction of 5-methylsulfonylthiophenes and the corresponding oxygen or sulfur anions. Small alkyl group substitution at the 5-position provided inhibitors equipotent with but possessing improved solubility.
MeSH terms
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Alkylation
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Amidines / chemical synthesis*
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Amidines / pharmacology*
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Indicators and Reagents
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Lithium Compounds / chemistry
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Protein Binding
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / pharmacology*
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Structure-Activity Relationship
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Thiazoles / chemical synthesis
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Thiazoles / pharmacology
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Thiophenes / chemical synthesis*
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Thiophenes / pharmacology*
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Urokinase-Type Plasminogen Activator / antagonists & inhibitors*
Substances
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Amidines
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Indicators and Reagents
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Lithium Compounds
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Serine Proteinase Inhibitors
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Thiazoles
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Thiophenes
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Urokinase-Type Plasminogen Activator