trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one | 86097-37-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
• 英文别名: 6-[2-(2,4-Dichloro-phenyl)-vinyl]-4-hydroxy-tetrahydro-pyran-2-one；(4R,6S)-6-[(E)-2-(2,4-dichlorophenyl)ethenyl]-4-hydroxyoxan-2-one
• CAS: 86097-37-2
• 化学式: C₁₃H₁₂Cl₂O₃
• 分子量: 287.142
• InChiKey: BGASINALMIKBMK-JTNORFRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one 在 二异丁基氢化铝 作用下， 生成
  参考文献：
  名称：

  手性合成子，甲基3-O-苄基-2,4,6-三苯氧基-6-碘-α-D-赤型己基吡喃糖苷在合成有效的HMG-CoA还原酶抑制剂中的用途

  摘要：

  化合物1是一种有效的合成HMG-CoA还原酶抑制剂，它是从手性合成子甲基3-O-苄基-2,4,6-三苯氧基-6-碘-α-D-赤型己吡喃糖苷合成的（2），利用新颖的钯介导的苄基醚裂解程序。

  DOI：

  10.1016/s0040-4039(00)98588-5
• 作为产物：
  描述：

  在 N-碘代丁二酰亚胺 、 四丁基碘化铵 作用下， 生成 trans-(E)-6-[2-(2,4-dichlorophenyl)ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one
  参考文献：
  名称：

  手性合成子，甲基3-O-苄基-2,4,6-三苯氧基-6-碘-α-D-赤型己基吡喃糖苷在合成有效的HMG-CoA还原酶抑制剂中的用途

  摘要：

  化合物1是一种有效的合成HMG-CoA还原酶抑制剂，它是从手性合成子甲基3-O-苄基-2,4,6-三苯氧基-6-碘-α-D-赤型己吡喃糖苷合成的（2），利用新颖的钯介导的苄基醚裂解程序。

  DOI：

  10.1016/s0040-4039(00)98588-5

文献信息

• Utilization of the chiral synthon, methyl 3-O-benzyl-2,4,6-trideoxy-6-iodo-α-D--hexopyranoside in the synthesis of a potent HMG-CoA reductase inhibitor
  作者：John D. Prugh、C.Stanley Rooney、Albert A. Deana、Harri G. Ramjit

  DOI：10.1016/s0040-4039(00)98588-5

  日期：1985.1

  Compound 1, a potent synthetic HMG-CoA reductase inhibitor, has been synthesized from the chiral synthon, methyl 3-O-benzyl-2,4,6-trideoxy-6-iodo-α-D-erythro-hexopyranoside (2), utilizing a novel palladium-mediated procedure for benzyl ether cleavage.

  化合物1是一种有效的合成HMG-CoA还原酶抑制剂，它是从手性合成子甲基3-O-苄基-2,4,6-三苯氧基-6-碘-α-D-赤型己吡喃糖苷合成的（2），利用新颖的钯介导的苄基醚裂解程序。
• 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. I. Structural modification of 5-substituted 3,5-dihydroxypentanoic acids and their lactone derivatives
  作者：G. E. Stokker、W. F. Hoffman、A. W. Alberts、E. J. Cragoe、A. A. Deana、J. L. Gilfillan、J. W. Huff、F. C. Novello、J. D. Prugh

  DOI：10.1021/jm00381a014

  日期：1985.3

  A series of 5-substituted 3,5-dihydroxypentanoic acids and their derivatives have been prepared and tested for inhibition of HMG-CoA reductase in vitro. In general, unless a carboxylate anion can be formed and the hydroxy groups remain unsubstituted in an erythro relationship, inhibitory activity is greatly reduced. Furthermore, only one enantiomer of the ring-opened form of lactone 6a(+/-) possesses

  已经制备了一系列5-取代的3，5-二羟基戊酸及其衍生物，并测试了其在体外对HMG-CoA还原酶的抑制作用。通常，除非可以形成羧酸根阴离子并且羟基以红邻关系保持未被取代，否则抑制活性会大大降低。此外，内酯6a（+/-）的开环形式的仅一种对映异构体具有外消旋体显示的活性。在5-甲醇部分和合适的亲脂性部分（例如2,4-二氯苯基）之间插入除乙基或（E）-乙烯基以外的桥联单元会减弱活性。
• 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。
• Structural modification of mevinolin
  作者：Ta Jyh Lee、Wilbur J. Holtz、Robert L. Smith

  DOI：10.1021/jo00145a029

  日期：1982.11