Synthesis and SAR of 4-Aryl-2-hydroxy-4-oxobut-2-enoic Acids and Esters and 2-Amino-4-aryl-4-oxobut-2-enoic Acids and Esters: Potent Inhibitors of Kynurenine-3-hydroxylase as Potential Neuroprotective Agents
| Autor: | Hind Sl, Drysdale Mj, Marilyn Jansen, John F. Reinhard |
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| Rok vydání: | 1999 |
| Předmět: |
Magnetic Resonance Spectroscopy
Ketone Stereochemistry Mitochondria Liver In Vitro Techniques Chemical synthesis Monocytes Mixed Function Oxygenases chemistry.chemical_compound Kynurenine 3-Monooxygenase Drug Discovery Animals Humans Enzyme Inhibitors chemistry.chemical_classification biology Aryl Rats Butyrates Kinetics Neuroprotective Agents Enzyme chemistry Enzyme inhibitor biology.protein Molecular Medicine Kynurenine Quinolinic acid |
| Zdroj: | Journal of Medicinal Chemistry. 43:123-127 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm990396t |
| Popis: | The synthesis and structure-activity relationship of a series of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids and esters and 2-amino-4-aryl-4-oxobut-2-enoic acids and esters as potent inhibitors of kynurenine-3-hydroxylase are described. These compounds are the most potent inhibitors of the kynurenine-3-hydroxylase enzyme so far disclosed. Additionally methyl 4-(3-chlorophenyl)-2-hydroxy-4-oxobut-2-enoate (2d), 4-(3-chlorophenyl)-2-hydroxy-4-oxobut-2-enoic acid (3d), methyl 4-(3-fluorophenyl)-2-hydroxy-4-oxobut-2-enoate (2f), and 4-(3-fluorophenyl)-2-hydroxy-4-oxobut-2-enoic acid (3f) prevent the increase in the interferon-gamma-induced synthesis of quinolinic acid in primary cultures of cultured human peripheral blood monocyte-derived macrophages. |
| Databáze: | OpenAIRE |
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