Abstract
We have previously reported that (4R,5R)-5-ethyl-2-imino-4-methylthiazolidine (3) strongly inhibits inducible nitric oxide synthase (iNOS). In a successive search for strong and selective iNOS inhibitors, we, herein, describe the synthesis of the selenium analogue of 3 (4: ES-2133) and its related optically active compounds and examine their in vitro and in vivo inhibitory activity against iNOS. In addition, an alternative synthetic method to the selected compound 4 and its pharmacokinetic profile is also reported.
MeSH terms
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Arginine / antagonists & inhibitors
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Biological Availability
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacokinetics*
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Kinetics
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Molecular Conformation
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase Type II
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Organoselenium Compounds / chemical synthesis*
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Organoselenium Compounds / chemistry
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Organoselenium Compounds / pharmacokinetics*
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Selenium / chemistry
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Organoselenium Compounds
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Arginine
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Selenium