Abstract
The synthesis and biological activity of a novel series of thrombin receptor antagonists is described. This series of compounds showed excellent in vitro and in vivo potency. The most potent compound 40 had an IC(50) of 7.6 nM and showed robust inhibition of platelet aggregation in a cynomolgus monkey model after oral administration.
MeSH terms
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Administration, Oral
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Alkaloids / chemistry
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Alkaloids / pharmacology*
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Animals
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Area Under Curve
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Chemistry, Pharmaceutical / methods*
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Furans / chemistry
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Furans / pharmacology*
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Inhibitory Concentration 50
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Ligands
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Macaca fascicularis
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Models, Chemical
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Naphthalenes / chemistry
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Naphthalenes / pharmacology*
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Parasympatholytics / chemistry
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Parasympatholytics / pharmacology*
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Piperidines / chemistry
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Piperidines / pharmacology*
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Platelet Aggregation / drug effects
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Protein Binding
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Rats
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Receptors, Thrombin / antagonists & inhibitors*
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Thrombin / chemistry
Substances
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Alkaloids
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Furans
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Ligands
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Naphthalenes
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Parasympatholytics
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Piperidines
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Receptors, Thrombin
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Thrombin
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himbacine