Abstract
We searched for non-nucleoside inhibitors of adenosine deaminase by rational structure-based de novo design and succeeded in the discovery of 1-(1-hydroxy-4-phenyl-2-butyl)imidazole-4-carboxamide (FR221647: K(i)=5.9 microM to human ADA) as a novel inhibitor with moderate activity and good pharmacokinetics compared with the known inhibitors pentostatin and EHNA.
MeSH terms
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Adenine / analogs & derivatives*
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Adenine / pharmacology
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Adenosine Deaminase Inhibitors*
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Administration, Oral
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Animals
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Area Under Curve
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydrogen Bonding
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Injections, Intraperitoneal
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Mice
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Models, Molecular
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Pentostatin / pharmacology
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Structure-Activity Relationship
Substances
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Adenosine Deaminase Inhibitors
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Enzyme Inhibitors
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Pentostatin
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9-(2-hydroxy-3-nonyl)adenine
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Adenine