methyl (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-5-hydroxy-3-oxo-6-heptenoate | 78443-77-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂醇
• 英文名称: methyl (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-5-hydroxy-3-oxo-6-heptenoate
• 英文别名: methyl (E)-7-(2,4-dichloro-6-phenylmethoxyphenyl)-5-hydroxy-3-oxo-6-heptenoate；methyl (E)-7-[2,4-dichloro-6-(phenylmethoxy)phenyl]-5-hydroxy-3-oxo-6-heptenoate；methyl (E)-7-(2,4-dichloro-6-phenylmethoxyphenyl)-5-hydroxy-3-oxohept-6-enoate
• CAS: 78443-77-3
• 化学式: C₂₁H₂₀Cl₂O₅
• 分子量: 423.293
• InChiKey: UFRNEEBJMQPUFL-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-5-hydroxy-3-oxo-6-heptenoate 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以99.5%的产率得到methyl (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-3,5-dihydroxy-6-heptenoate
  参考文献：
  名称：

  3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 2. Structural modification of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives

  摘要：

  A series of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic (heptanoic) acids and their lactone derivatives have been prepared and tested for inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in vitro. A systematic exploration of the structure-activity relationships in this series led to the synthesis of (+)-trans-(E)-6-[2-[2,4-dichloro-6-[(4-fluorophenyl) methoxyl]phenyl]ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (66(+)), which has one-half of the inhibitory activity of compactin.

  DOI：

  10.1021/jm00152a001
• 作为产物：
  描述：

  2,4-dichloro-6-(phenylmethoxy)benzaldehyde 在 正丁基锂 、 sodium hydride 作用下， 反应 2.0h， 生成 methyl (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-5-hydroxy-3-oxo-6-heptenoate
  参考文献：
  名称：

  3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 2. Structural modification of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives

  摘要：

  A series of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic (heptanoic) acids and their lactone derivatives have been prepared and tested for inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in vitro. A systematic exploration of the structure-activity relationships in this series led to the synthesis of (+)-trans-(E)-6-[2-[2,4-dichloro-6-[(4-fluorophenyl) methoxyl]phenyl]ethyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (66(+)), which has one-half of the inhibitory activity of compactin.

  DOI：

  10.1021/jm00152a001
• 作为试剂：
  描述：

  3-(3,4-二氯苯基)丙-2-烯醛 以 methyl (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-5-hydroxy-3-oxo-6-heptenoate 为溶剂， 生成 (E)-6-[2-(3,4-Dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
  参考文献：
  名称：

  Substituted pyranone inhibitors of cholesterol synthesis

  摘要：

  甲基、乙基、正丙基、2-(乙酰氨基)乙基或1-(2,3-二羟基)丙基酯是E-(3R,5S)-7-(4'-氟-3,3',5-三甲基[1,1'-联苯基]-2-基)-3,5-二羟基-6-庚二烯酸的结构式：这些是HMG-CoA还原酶抑制剂，可用于治疗与高胆固醇血症相关的疾病。

  公开号：

  US04567289A1

文献信息

• Cis/trans isomerization of
  申请人：Merck & Co., Inc.

  公开号：US04308378A1

  公开（公告）日：1981-12-29

  Biologically inactive cis-6-(substituted-arylethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-on es are isomerized to the corresponding anti-hypercholesterolemic trans-isomers by heating in the presence of a heavy metal salt.

  生物学上无活性的顺式6-(取代芳基乙烯基)-3,4,5,6-四氢-4-羟基-2H-吡喃-2-酮在存在重金属盐的情况下加热，发生异构化为相应的抗高胆固醇反式异构体。
• Pharmaceutical composition useful for the treatment of hypercholesteremia
  申请人：Merck & Co., Inc.

  公开号：EP0010299A1

  公开（公告）日：1980-09-17

  Pharmaceutical composition, useful for the treatment of hypercholesteremia in mammals, especially humans, comprising (a) a cholesterol synthesis inhibitor acting at the HMG-CoA reductase level with an EO,. less than 10-°, such as a 6-[2-(8-substituted- 2-methyl-1,2,6,7,8,8a -hexahydro-1-naphthyl) ethyl)-4-hydroxy-4, 5-dihydro-2-pyrone or a 4R trans-6-phenyi-E-4-hydroxytetrahydropyran-2-one in which E is a bond, a C1-) alkylene or-CH =CH- and (b) a non-toxic anion exchange resin in the weight ratio of 1:0.08 to 1:15,000. The resin preferably is a styrene-divinylbenzene copolymer containing quaternary ammonium groups. When present in the indicated weight ratios, synergism exists between the cholesterol synthesis inhibitor and the anion exchange resin. The components can be present separately for separate dosages or, preferably, as a unitary combination. The effects of treatments with compound II (Compacun) and with cholestyramine, separately and in combination, are illustrated by figure 1.

  用于治疗哺乳动物，尤其是人类高胆固醇血症的药物组合物，包括 (a) 在 HMG-CoA 还原酶水平起作用的胆固醇合成抑制剂，其 EO小于 10-°，如 6-[2-(8-取代-2-甲基-1,2,6,7,8,8a-六氢-1-萘基)乙基)-4-羟基-4、5-二氢-2-吡喃酮或 4R 反式-6-苯基-E-4-羟基四氢吡喃-2-酮，其中 E 为键、C1-)亚烷基或-CH =CH- 和 (b) 无毒阴离子交换树脂，重量比为 1：0.08 至 1:15,000 的重量比。树脂最好是含有季铵基团的苯乙烯-二乙烯基苯共聚物。当以所述重量比存在时，胆固醇合成抑制剂和阴离子交换树脂之间会产生协同作用。这些成分可以分别以不同的剂量存在，也可以作为一个整体组合存在。图 1 说明了化合物 II（康帕康）和胆甾胺单独或组合使用的效果。
• STOKKER, G. E.
  作者：STOKKER, G. E.

  DOI：——

  日期：——
• WILLARD, A. K.;NOVELLO, F. C.;HOFFMAN, W. F.;CRAGOE, E. J. ,, JR
  作者：WILLARD, A. K.、NOVELLO, F. C.、HOFFMAN, W. F.、CRAGOE, E. J. ,, JR

  DOI：——

  日期：——
• WILLARD, A. K.;NOVELLO, F. C.;HOFFMAN, W. F.;CRAGOE, E. J. ,, JR.
  作者：WILLARD, A. K.、NOVELLO, F. C.、HOFFMAN, W. F.、CRAGOE, E. J. ,, JR.

  DOI：——

  日期：——