Abstract
1-Benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole (28, YC-1) was selected as the lead compound for systemic structural modification. After screening for antiplatelet activity, SARs of YC-1 analogues were established. Among these potent active derivatives, compounds 29, 30, 31, 44, and 45 functioned as potent activators of sGC and inhibitors of PDE5 with potency comparable to that of YC-1. In addition, compound 58 was found to be a selective and potent inhibitor of protease-activated receptor type 4 (PAR4)-dependent platelet activation.
MeSH terms
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3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors
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Cyclic Nucleotide Phosphodiesterases, Type 5
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Enzyme Activation
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Guanylate Cyclase
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Humans
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In Vitro Techniques
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Indazoles / chemical synthesis*
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Indazoles / chemistry
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Indazoles / pharmacology
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Platelet Activation / drug effects
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Platelet Aggregation Inhibitors / chemical synthesis*
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Platelet Aggregation Inhibitors / chemistry
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Platelet Aggregation Inhibitors / pharmacology
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Thrombin / antagonists & inhibitors
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Soluble Guanylyl Cyclase
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Indazoles
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Platelet Aggregation Inhibitors
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Receptors, Cytoplasmic and Nuclear
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Receptors, Thrombin
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3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
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3',5'-Cyclic-GMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 5
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PDE5A protein, human
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Guanylate Cyclase
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Soluble Guanylyl Cyclase
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protease-activated receptor 4