Abstract
Metabolic stabilization of the chemical lead 1, which is a structurally novel inhibitor of TNF-alpha production, was accomplished by introducing a (1S)-methyl group into the optically active backbone. As a result, 2, 3 and 4 were identified as drug candidates and evaluated pharmacologically. The analysis of an active conformer was also carried out.
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / chemical synthesis*
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Adjuvants, Immunologic / pharmacology
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Animals
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Benzylamines / administration & dosage
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Benzylamines / chemical synthesis
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Benzylamines / pharmacology
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Female
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Lipopolysaccharides / administration & dosage
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Male
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Mice
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Mice, Inbred BALB C
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Survival Rate
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Adjuvants, Immunologic
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Benzylamines
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Lipopolysaccharides
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Tumor Necrosis Factor-alpha