4-(4-Cyano-phenyl)-5-(4-fluoro-phenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester | 135834-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-(4-Cyano-phenyl)-5-(4-fluoro-phenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester
• 英文别名: 4-(4-Cyano-phenyl)-5-(4-fluoro-phenyl)-1-[2-(4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester；ethyl 4-(4-cyanophenyl)-5-(4-fluorophenyl)-1-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-2-propan-2-ylpyrrole-3-carboxylate
• CAS: 135834-12-7
• 化学式: C₃₀H₃₁FN₂O₅
• 分子量: 518.585
• InChiKey: IYDDXEIYERNMIL-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl α-bromo-4-fluorobenzeneacetate 在 盐酸 、 sodium hydroxide 、 水 、 乙酸酐 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 27.0h， 生成 4-(4-Cyano-phenyl)-5-(4-fluoro-phenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran 2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus

  摘要：

  A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl)ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33, (+)-(4R)-trans-2-(4-fluorophenyl)-5-(1-methylethyl)-N,3-diphenyl-1-[(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4-carboxamide) with five times the inhibitory potency of the fungal metabolite compactin.

  DOI：

  10.1021/jm00105a056

文献信息

• Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran 2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus
  作者：Bruce D. Roth、C. J. Blankley、A. W. Chucholowski、E. Ferguson、M. L. Hoefle、D. F. Ortwine、R. S. Newton、C. S. Sekerke、D. R. Sliskovic、M Wilson

  DOI：10.1021/jm00105a056

  日期：1991.1

  A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl)ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33, (+)-(4R)-trans-2-(4-fluorophenyl)-5-(1-methylethyl)-N,3-diphenyl-1-[(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4-carboxamide) with five times the inhibitory potency of the fungal metabolite compactin.