A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) inhibitors.One member of this series,(4R,6S)-6-...A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) inhibitors.One member of this series,(4R,6S)-6-{(E)-2-[6-fluoro-7-chloro-4-(4-fluorophenoxy-quinoline)-3-yl-]-ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (3d),showed more potent activity than rosuvastatin or pitavastatin to inhibit the rat HMG CoA reductase in vitro.This compound was selected for the extensive preclinical development as a potential hypocholesterolemic candidate.展开更多
基金The State New Drug Innovation (Grant No. 2009ZX09301-007)Shanghai Rising-Star Program (Grant No. 08QB1403800)Shanghai Innovation Action Project (Grant No. 09431901300)
文摘A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) inhibitors.One member of this series,(4R,6S)-6-{(E)-2-[6-fluoro-7-chloro-4-(4-fluorophenoxy-quinoline)-3-yl-]-ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (3d),showed more potent activity than rosuvastatin or pitavastatin to inhibit the rat HMG CoA reductase in vitro.This compound was selected for the extensive preclinical development as a potential hypocholesterolemic candidate.