Quantitative structure-activity relationships involving the inhibition of glycolic acid oxidase by derivatives of glycolic and glyoxylic acids
| Autor: | Haydn W. R. Williams, W. C. Randall, Paul S. Anderson, Eva Eichler, Stuart R. Michelson, Edward J. Cragoe, Emlen L. Cresson, Kermit B. Streeter, C. Stanley Rooney, Harvey Schwam |
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| Rok vydání: | 1979 |
| Předmět: |
chemistry.chemical_classification
Glycolic acid oxidase Stereochemistry Swine Glyoxylate cycle Quantitative structure Glyoxylates Acetates In Vitro Techniques Keto Acids Phenoxyacetates Oxalate Glycolates chemistry.chemical_compound Alcohol Oxidoreductases Structure-Activity Relationship Enzyme chemistry Nucleophile Liver Drug Discovery Pi Molecular Medicine Organic chemistry Animals |
| Zdroj: | Journal of medicinal chemistry. 22(6) |
| ISSN: | 0022-2623 |
| Popis: | The enzyme glycolic acid oxidase oxidizes glycolate to glyoxylate and glyoxylate to oxalate. Three series of compounds related to the natural substrates, substituted glycolic, oxyacetic, and glyoxylic acids, have been investigated as inhibitors of this enzyme using the techniques of regression analysis and quantitative structure-activity relationships. The best overall correlation with inhibitory potencies was found with the Hansch hydrophobic parameter pi. The classical electronic parameters sigmap, sigmam, F, and R performed poorly. For the substituted glyoxylic acids, a dummy parameter relating to the presence of a nucleophilic group in close proximity to the alpha-carbonyl of the glyoxylate group was found to be highly significant. The syntheses of six novel glycolic and glyoxylic acids are described. |
| Databáze: | OpenAIRE |
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