Abstract
A novel series of 2-cyclopropyl-4-thiophenyl quinoline-based mevalonolactones were synthesized from the substituted anilines by several reactions. Among them, (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(4-fluoro-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1d), (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1f) and (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4,7-di(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1q) showed potent HMG-CoA reductase inhibitory activity comparable with pitavastatin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyl Coenzyme A / antagonists & inhibitors
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Acyl Coenzyme A / metabolism*
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Animals
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Cyclopropanes / chemical synthesis*
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Cyclopropanes / chemistry
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Cyclopropanes / pharmacology
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemical synthesis*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Liver / metabolism
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Magnetic Resonance Spectroscopy
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Mevalonic Acid / analogs & derivatives*
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Mevalonic Acid / chemical synthesis
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Mevalonic Acid / chemistry
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Mevalonic Acid / pharmacology
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Quinolines / pharmacology
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Rats
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Spectrometry, Mass, Electrospray Ionization
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Sulfhydryl Compounds / chemical synthesis*
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / pharmacology
Substances
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Acyl Coenzyme A
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Cyclopropanes
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Quinolines
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Sulfhydryl Compounds
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3-hydroxy-3-methylglutaryl-coenzyme A
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mevalonolactone
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Mevalonic Acid