Synthesis and HMG-CoA reductase inhibition of 2-cyclopropyl-4-thiophenyl-quinoline mevalonolactones.
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.
Zhao
Shikui
S
State Key Lab of New Drug & Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, PR China. zhaosk2002@163.com
Zhou
Weicheng
W
Liu
Jun
J
D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000214:Acyl Coenzyme A; D003521:Cyclopropanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D013438:Sulfhydryl Compounds; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; C015367:mevalonolactone; D008798:Mevalonic Acid