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
The crystal structure of the title compound(E)-ethyl 2-(4-(2,4-dimethoxy benzylide-neamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-3-ylthio)acetate(4,C_(24)H_(28)N_(4)O_(7)S,Mr=516.17)was synthesized and determin...The crystal structure of the title compound(E)-ethyl 2-(4-(2,4-dimethoxy benzylide-neamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-3-ylthio)acetate(4,C_(24)H_(28)N_(4)O_(7)S,Mr=516.17)was synthesized and determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P2_(1)/n with a=13.162(2),b=8.4506(13),c=22.602(4)Å,β=99.888(3)°,μ=0.183 mm^(-1),V=2476.5(7)Å^(3),Z=4,D_(c)=1.385 g/cm^(3),F(000)=1088,T=110(2)K,R=0.0426 and wR=0.1216 for 3859 observed reflections with I 2σ(Ⅰ).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.
基金supported by the Science Foundation of the Southern Medical University for New Excellent Talents(No.B1000374)the Natural Science Foundation of Guangdong Province(No.10451051501004725)
文摘The crystal structure of the title compound(E)-ethyl 2-(4-(2,4-dimethoxy benzylide-neamino)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-3-ylthio)acetate(4,C_(24)H_(28)N_(4)O_(7)S,Mr=516.17)was synthesized and determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P2_(1)/n with a=13.162(2),b=8.4506(13),c=22.602(4)Å,β=99.888(3)°,μ=0.183 mm^(-1),V=2476.5(7)Å^(3),Z=4,D_(c)=1.385 g/cm^(3),F(000)=1088,T=110(2)K,R=0.0426 and wR=0.1216 for 3859 observed reflections with I 2σ(Ⅰ).
