(E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-3,5-dihydroxy-6-heptenoic acid | 78443-79-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂醇
• 英文名称: (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-3,5-dihydroxy-6-heptenoic acid
• 英文别名: (E)-7-(2,4-Dichloro-6-phenylmethoxyphenyl)-3,5-dihydroxy-6-heptenoic acid；(E)-7-(2,4-dichloro-6-phenylmethoxyphenyl)-3,5-dihydroxyhept-6-enoic acid
• CAS: 78443-79-5；121308-27-8
• 化学式: C₂₀H₂₀Cl₂O₅
• 分子量: 411.282
• InChiKey: KHWYMLRZXHMZLC-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-3,5-dihydroxy-6-heptenoic acid 生成 trans-(E)-6-[2-(2,4-dichloro-6-phenylmethoxyphenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
  参考文献：
  名称：

  STOKKER, G. E.

  摘要：

  DOI：
• 作为产物：
  描述：

  (E)-3-<2,4-dichloro-6-(phenylmethoxy)phenyl>-2-propenal 在 sodium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 (E)-7-<2,4-dichloro-6-(phenylmethoxy)phenyl>-3,5-dihydroxy-6-heptenoic acid
  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

文献信息

• Substituted pyranone inhibitors of cholesterol synthesis
  申请人：Merck & Co., Inc.

  公开号：US04375475A1

  公开（公告）日：1983-03-01

  6-Phenyl-, phenylalkyl- and phenylethenyl-4-hydroxytetrahydropyran-2-ones in the 4(R)-trans stereoisomeric forms are potent inhibitors of cholesterol synthesis by virtue of their ability to inhibit the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

  4(R)-反式立体异构形式的6-苯基、苯基烷基和苯乙烯基-4-羟基四氢吡喃-2-酮是胆固醇合成的有效抑制剂，因为它们能够抑制酶3-羟基-3-甲基戊二酰辅酶A还原酶。
• 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。
• Substituted 6-Phenethyl-and phenylethenyl-3,4,5,6-tetrahydro-4-hydroxytetraydropyran-2-ones in the4-R trans stereoisomeric forms and the corresponding dihydroxy acids, process for preparing and pharmaceutical composition comprising them
  申请人：Merck & Co., Inc.

  公开号：EP0024348A1

  公开（公告）日：1981-03-04

  6-Phenyl-, phenalkyl- and phenylethenyl-4-hydroxytetrahydropyran-2-ones in the 4- R trans stereoisomeric forms having the structure wherein A is H or methyl; E is a direct bond, -CH2-, -CH2-CH2-, -CH2-CH2-CH2- or-CH-CH-; and R1, R2 and R3 have several meanings, and the corresponding dihydroxy acids in which the lactone ring is hydrolytically opened, and the pharmaceutically acceptable salts of said dihydroxy acids, and the lower alkyl and the phenyl, dimethylamino or acetylamino-substituted lower alkyl esters of said dihydroxy acids; and processes for preparing them. These compounds are potent inhibitors of cholesterol synthesis by the enzyme hydroxymethyl glutaryl coenzyme A reductase.

  6-苯基、苯基烷基和苯基乙烯基-4-羟基四氢吡喃-2-酮的 4- R 反式立体异构体，其结构为 其中 A 是 H 或甲基 E为直接键、-CH2-、-CH2-CH2-、-CH2-CH2-或-CH-CH-；R1、R2和R3有多种含义，以及相应的内酯环被水解打开的二羟基酸、所述二羟基酸的药学上可接受的盐、所述二羟基酸的低级烷基和苯基、二甲基氨基或乙酰氨基取代的低级烷基酯；以及制备它们的工艺。这些化合物是羟甲基戊二酰辅酶 A 还原酶合成胆固醇的强效抑制剂。
• STOKKER, G. E.
  作者：STOKKER, G. E.

  DOI：——

  日期：——