1-(4-氟苯基)-5-甲基-1,4-己二酮 | 104568-68-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(4-氟苯基)-5-甲基-1,4-己二酮
• 英文名称: 1-(4-fluorophenyl)-5-methyl-1,4-hexanedione
• 英文别名: 1-(4-fluorophenyl)-5-methylhexane-1,4-dione
• CAS: 104568-68-5
• 化学式: C₁₃H₁₅FO₂
• mdl: MFCD25953389
• 分子量: 222.259
• InChiKey: WYAWZJWKVWBATK-UHFFFAOYSA-N

物化性质

• 沸点：
  338.5±22.0 °C(Predicted)
• 密度：
  1.083±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-氟苯基)-5-甲基-1,4-己二酮 在 吡啶 、 溶剂黄146 、 potassium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 3-[2-(4-Fluoro-phenyl)-5-isopropyl-pyrrol-1-yl]-butyronitrile
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 1. trans-6-(2-Pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a novel series of HMG-CoA reductase inhibitors. 1. Effects of structural modifications at the 2- and 5-positions of the pyrrole nucleus

  摘要：

  A novel series of trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones and their dihydroxy acid derivatives were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. A systematic study of substitution at the 2- and 5-positions of the pyrrole ring revealed that optimum potency was realized with the 2-(4-fluorophenyl)-5-isopropyl derivative 8x, which possessed 30% of the in vitro activity of the potent fungal metabolite compactin (I). A molecular modeling analysis led to the description of a pharmacophore model characterized by (A) length limits of 5.9 and 3.3 A for the 2- and 5-substituents, respectively, as well as an overall width limit of 10.6 A across the pyrrole ring from the 2- to the 5-substituent and (B) an orientation of the ethyl(ene) bridge to the 4-hydroxypyran-2-one ring nearly perpendicular to the planes of the parent pyrrole, hexahydronaphthalene, and phenyl rings of the structures examined (Figure 3, theta = 80-110 degrees). Attempts to more closely mimic compactin's polar isobutyric ester side chain with the synthesis of 2-phenylpyrroles containing polar phenyl substituents resulted in analogues with equal or slightly reduced potencies when compared to the 2-[(unsubstituted or 4-fluoro)phenyl]pyrroles, supporting the hypothesis that inhibitory potency is relatively insensitive to side-chain polarity or charge distribution in this area.

  DOI：

  10.1021/jm00163a005
• 作为产物：
  描述：

  4-甲基-1-戊烯-3-酮 、 对氟苯甲醛 在 2-(2-hydroxyethyl)-3-methyl-4-benzylthiazolium chloride 、 三乙胺 作用下， 反应 5.0h， 以2.6 g的产率得到1-(4-氟苯基)-5-甲基-1,4-己二酮
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 1. trans-6-(2-Pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a novel series of HMG-CoA reductase inhibitors. 1. Effects of structural modifications at the 2- and 5-positions of the pyrrole nucleus

  摘要：

  A novel series of trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones and their dihydroxy acid derivatives were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. A systematic study of substitution at the 2- and 5-positions of the pyrrole ring revealed that optimum potency was realized with the 2-(4-fluorophenyl)-5-isopropyl derivative 8x, which possessed 30% of the in vitro activity of the potent fungal metabolite compactin (I). A molecular modeling analysis led to the description of a pharmacophore model characterized by (A) length limits of 5.9 and 3.3 A for the 2- and 5-substituents, respectively, as well as an overall width limit of 10.6 A across the pyrrole ring from the 2- to the 5-substituent and (B) an orientation of the ethyl(ene) bridge to the 4-hydroxypyran-2-one ring nearly perpendicular to the planes of the parent pyrrole, hexahydronaphthalene, and phenyl rings of the structures examined (Figure 3, theta = 80-110 degrees). Attempts to more closely mimic compactin's polar isobutyric ester side chain with the synthesis of 2-phenylpyrroles containing polar phenyl substituents resulted in analogues with equal or slightly reduced potencies when compared to the 2-[(unsubstituted or 4-fluoro)phenyl]pyrroles, supporting the hypothesis that inhibitory potency is relatively insensitive to side-chain polarity or charge distribution in this area.

  DOI：

  10.1021/jm00163a005

文献信息

• Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of
  申请人：Warner-Lambert Company

  公开号：US04647576A1

  公开（公告）日：1987-03-03

  6-[2-(Substituted-pyrrol-1-yl)alkyl]pyran-2-ones and the corresponding ring-opened hydroxy-acids derived therefrom are potent inhibitors of the enzyme 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA reductase), and are thus useful hypolipidemic and hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of treatment employing such pharmaceutical compositions are also disclosed.

  6-[2-(取代吡咯-1-基)烷基]吡喃-2-酮及其相应的开环羟基酸是酶3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）的有效抑制剂，因此可用作降脂和降胆固醇药物。含有这些化合物的药物组合物，以及使用这些药物组合物的治疗方法也被揭示。
• Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0179559A2

  公开（公告）日：1986-04-30

  6-[2-lSubstituted-pyrrol-1-yl)alkyl]pyran-2-ones of formula I and the corresponding ring-opened hydroxy-acids derived therefrom are potent inhibitors of the enzyme 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA reductase), and are thus useful hypolipidemic and hypocholesterolemic agents. Pharmaceutical compositions containing such compounds. and a method of preparing the compounds are also disclosed.

  式 I 的 6-[2-取代-吡咯-1-基)烷基]吡喃-2-酮 及其衍生的相应开环羟基酸是 3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMG-CoA 还原酶）的强效抑制剂，因此是有用的降血脂和降胆固醇药物。此外，还公开了含有此类化合物的药物组合物以及制备这些化合物的方法。
• ——
  作者：HOEFLE M. L.、 ROTH B. D.、 STRATTON C. D.

  DOI：——

  日期：——
• US4647576A
  申请人：——

  公开号：US4647576A

  公开（公告）日：1987-03-03
• Inhibitors of cholesterol biosynthesis. 1. trans-6-(2-Pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a novel series of HMG-CoA reductase inhibitors. 1. Effects of structural modifications at the 2- and 5-positions of the pyrrole nucleus
  作者：Bruce D. Roth、D. F. Ortwine、M. L. Hoefle、C. D. Stratton、D. R. Sliskovic、M. W. Wilson、R. S. Newton

  DOI：10.1021/jm00163a005

  日期：1990.1

  A novel series of trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones and their dihydroxy acid derivatives were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. A systematic study of substitution at the 2- and 5-positions of the pyrrole ring revealed that optimum potency was realized with the 2-(4-fluorophenyl)-5-isopropyl derivative 8x, which possessed 30% of the in vitro activity of the potent fungal metabolite compactin (I). A molecular modeling analysis led to the description of a pharmacophore model characterized by (A) length limits of 5.9 and 3.3 A for the 2- and 5-substituents, respectively, as well as an overall width limit of 10.6 A across the pyrrole ring from the 2- to the 5-substituent and (B) an orientation of the ethyl(ene) bridge to the 4-hydroxypyran-2-one ring nearly perpendicular to the planes of the parent pyrrole, hexahydronaphthalene, and phenyl rings of the structures examined (Figure 3, theta = 80-110 degrees). Attempts to more closely mimic compactin's polar isobutyric ester side chain with the synthesis of 2-phenylpyrroles containing polar phenyl substituents resulted in analogues with equal or slightly reduced potencies when compared to the 2-[(unsubstituted or 4-fluoro)phenyl]pyrroles, supporting the hypothesis that inhibitory potency is relatively insensitive to side-chain polarity or charge distribution in this area.