Abstract
Treatment of N(alpha)-Cbz-N(epsilon)-(2-hydroxyethylaminothiocarbonyl)-L-lysine N-(2-hydroxyethyl)amide with boiling hydrochloric acid gave N(epsilon)-(4,5-dihydrothiazol-2-yl)-L-lysine. This was a weak and non-isoform selective inhibitor of NOS, whereas N(epsilon)-aminothiocarbonyl-L-lysine and its methyl ester were potent, with IC(50)=13 and 18 microM, respectively, against human iNOS and IC(50)=3 and 8 microM, respectively, against rat nNOS. Time dependence was observed for inhibition of nNOS by the ester.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Citrulline / analogs & derivatives*
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Citrulline / pharmacology*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Indicators and Reagents
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Isoenzymes / antagonists & inhibitors
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Kinetics
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Magnetic Resonance Spectroscopy
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type II
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Rats
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Recombinant Proteins / chemistry
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Structure-Activity Relationship
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Substrate Specificity
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Thiourea / analogs & derivatives*
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Thiourea / pharmacology*
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omega-N-Methylarginine / pharmacology
Substances
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Enzyme Inhibitors
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Indicators and Reagents
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Isoenzymes
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Recombinant Proteins
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thiocitrulline
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omega-N-Methylarginine
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Citrulline
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NOS1 protein, human
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nitric Oxide Synthase Type II
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Nos1 protein, rat
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Nos2 protein, rat
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Thiourea