Abstract
A new series of 1-(1,3-benzodioxol-5-ylmethyl)-3-[4-(1H-Imidazol-1-yl)phenoxy]-piperidine analogs were designed and identified as potent and selective inhibitors of NO formation based both on the crystal structure of a murine iNOS Delta114 monomer domain/ inhibitor complex and inhibition of the NO formation in human A172 cell assays. Compound 12S showed high potency and high iNOS selectivity versus nNOS and eNOS.
MeSH terms
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Animals
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Cell Line, Tumor
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Chemistry, Pharmaceutical / methods*
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Dimerization
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / pharmacology
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Inhibitory Concentration 50
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Mice
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Models, Chemical
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Molecular Conformation
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Nitric Oxide / antagonists & inhibitors*
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Nitric Oxide Synthase Type I / antagonists & inhibitors
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Nitric Oxide Synthase Type II / antagonists & inhibitors*
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Nitric Oxide Synthase Type III / antagonists & inhibitors
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology
Substances
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1-(1,3-benzodioxol-5-ylmethyl)-3-(4-(1H-imidazol-1-yl)phenoxy)-piperidine
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Enzyme Inhibitors
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Imidazoles
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Piperidines
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Nitric Oxide
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III