trans-6-[2-[2-(4-Fluorophenyl)-3,4-dimethyl-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: trans-6-[2-[2-(4-Fluorophenyl)-3,4-dimethyl-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one
• 英文别名: 6-{2-[2-(4-Fluoro-phenyl)-5-isopropyl-3,4-dimethyl-pyrrol-1-yl]-ethyl}-4-hydroxy-tetrahydro-pyran-2-one；(4R,6R)-6-[2-[2-(4-fluorophenyl)-3,4-dimethyl-5-propan-2-ylpyrrol-1-yl]ethyl]-4-hydroxyoxan-2-one
• 化学式: C₂₂H₂₈FNO₃
• 分子量: 373.468
• InChiKey: KHNPIGQSDPPQFX-RTBURBONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-<2-(1,3-dioxolan-2-yl)ethyl>-N-(4-fluorobenzoyl)-DL-valine 在 三乙基硅烷 、 lithium aluminium tetrahydride 、 水 、 乙酸酐 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 4.5h， 生成 trans-6-[2-[2-(4-Fluorophenyl)-3,4-dimethyl-5-(1-methylethyl)-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one
  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

• 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。
• US4647576A
  申请人：——

  公开号：US4647576A

  公开（公告）日：1987-03-03
• US4775681A
  申请人：——

  公开号：US4775681A

  公开（公告）日：1988-10-04
• 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.