Inhibitors of cholesterol biosynthesis. 4. trans-6-[2-(substituted-quinolinyl)ethenyl/ethyl]tetrahydro-4-hydroxy-2 H-pyran-2-ones, a novel series of HMG-CoA reductase inhibitors
| Autor: | M. K. Shaw, E. Ferguson, W. H. Roark, J. A. Picard, Bruce David Roth, Catherine Sekerke, Roger S. Newton, Drago Robert Sliskovic, B.R. Krause |
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| Rok vydání: | 1991 |
| Předmět: |
Stereochemistry
Reductase chemistry.chemical_compound Structure-Activity Relationship In vivo Drug Discovery Potency Animals chemistry.chemical_classification biology Molecular Structure Chemistry Anticholesteremic Agents Quinoline Rats Enzyme Liver Enzyme inhibitor Pyran Pyrones HMG-CoA reductase biology.protein Quinolines Molecular Medicine Indicators and Reagents Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | Journal of medicinal chemistry. 34(1) |
| ISSN: | 0022-2623 |
| Popis: | A series of substituted quinoline mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and (cholesterol biosynthesis) in vivo. Since previous studies suggested that the 4-(4-fluorophenyl) and 2-(1-methylethyl) substituents afforded optimum potency, attention was focused on variations at position 6 of the quinoline ring. Biological evaluation of a small number of analogues bearing a variety of 6-substituents showed that modification at this position had little effect on potency. Several compounds (8b, 8e, and 11) were identified that showed comparable potency to compactin and mevinolin in both the in vitro and in vivo assays. |
| Databáze: | OpenAIRE |
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