Abstract
Dihydropyridin-2-imines were synthesized and biologically evaluated both in vitro and in vivo using a nitric oxide inhibition assay. Compounds 1, 4, 5 and 7-11 exhibited potent activity in the inducible nitric oxide (iNOS) inhibition assay. Of these 5, 6, 9 and 10 showed 5- to 11-fold increases in isoform selectivity. Compounds 1, 5, 9 and 10 showed potent inhibitory activity in the NOx accumulation assay in mice. Compounds 1 and 5 also showed good bioavailability (BA) when given orally.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Dihydropyridines / chemical synthesis
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Dihydropyridines / pharmacokinetics*
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Dihydropyridines / pharmacology
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Drug Design
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Drug Evaluation, Preclinical
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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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Imines / chemical synthesis
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Imines / pharmacokinetics
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Imines / pharmacology
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Lipopolysaccharides / administration & dosage
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Maximum Tolerated Dose
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Mice
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Nitric Oxide / blood
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase Type II
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Structure-Activity Relationship
Substances
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Dihydropyridines
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Enzyme Inhibitors
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Imines
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Lipopolysaccharides
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Nitric Oxide
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse