Abstract
Guided by available X-ray crystal structure data on the serine protease thrombin, a series of pyridin-2-one derivatives were designed and synthesized having diverse functionality at the P(1) and P(3) sites. Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found for selected analogues.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry
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Crystallography, X-Ray
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Drug Design*
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Humans
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Models, Molecular
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Molecular Structure
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Protein Binding
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Protein Structure, Tertiary
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / pharmacology*
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Structure-Activity Relationship
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Sulfonamides / chemistry
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Thrombin / antagonists & inhibitors*
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Thrombin / metabolism
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Trypsin / chemistry
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Trypsin / metabolism
Substances
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Amines
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Pyridones
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Sulfonamides
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2-hydroxypyridine
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Trypsin
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Thrombin