3-(2-Bicyclo[2.2.2]oct-5-en-2-yl-5-methyl-pyrrol-1-yl)-propionitrile | 123184-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3-(2-Bicyclo[2.2.2]oct-5-en-2-yl-5-methyl-pyrrol-1-yl)-propionitrile
• CAS: 123184-36-1
• 化学式: C₁₆H₂₀N₂
• 分子量: 240.348
• InChiKey: WVOQRRSDUQNFAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  28.72
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-(2-Bicyclo[2.2.2]oct-5-en-2-yl-5-methyl-pyrrol-1-yl)-propionitrile 在 盐酸 、 二异丁基氢化铝 作用下， 生成 (4R,6R)-6-[2-(2-Bicyclo[2.2.2]oct-5-en-2-yl-5-methyl-pyrrol-1-yl)-ethyl]-4-hydroxy-tetrahydro-pyran-2-one
  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：

  1-Bicyclo[2.2.2]oct-5-en-2-yl-propenone 在 2-(2-hydroxyethyl)-3-methyl-4-benzylthiazolium chloride 、 对甲苯磺酸 、 三乙胺 作用下， 以 溶剂黄146 为溶剂， 反应 20.0h， 生成 3-(2-Bicyclo[2.2.2]oct-5-en-2-yl-5-methyl-pyrrol-1-yl)-propionitrile
  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