Abstract
A new class of selective FXIIIa inhibitors with a bicyclic [1,2,4]-thiadiazole pharmacophore is described. At 160 muM, compound 8 caused 50% reduction in fibrin gamma-chain cross-linking and suppressed the polymerization of alpha chains in platelet-depleted human plasma clots. Fibrinolysis rates in response to tissue plasminogen activator were directly proportional to the concentration of 8 in plasma at the time of clotting.
MeSH terms
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Animals
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Factor XIII / antagonists & inhibitors*
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Factor XIII / chemistry
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Fibrinolytic Agents / chemical synthesis*
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Fibrinolytic Agents / chemistry
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Fibrinolytic Agents / pharmacology
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Guinea Pigs
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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In Vitro Techniques
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Kinetics
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Structure-Activity Relationship
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Thiadiazoles / chemical synthesis*
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Thiadiazoles / chemistry
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Thiadiazoles / pharmacology
Substances
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Fibrinolytic Agents
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Imidazoles
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Thiadiazoles
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Factor XIII