methyl 7-<2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-<(phenylamino)carbonyl>-1H-pyrrol-1-yl>-5-hydroxy-3-oxo-1-heptanoate | 110862-47-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: methyl 7-<2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-<(phenylamino)carbonyl>-1H-pyrrol-1-yl>-5-hydroxy-3-oxo-1-heptanoate
• 英文别名: 2-(4-fluorophenyl)-δ-hydroxy-5-(1-methylethyl)-β-oxo-3-phenyl-4-[(phenylamino)carbonyl]-1 H-pyrrole-1-heptanoic acid, methyl ester；2-(4-fluorophenyl)-δ-hydroxy-5-(1-methylethyl)-β-oxo-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, methyl ester；2-(4-fluorophenyl)-δ-hydroxy-5-(1-methylethyl)-β-oxo-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid,methyl ester；methyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-5-hydroxy-3-oxoheptanoate；methyl 7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-5-hydroxy-3-oxoheptanoate
• CAS: 110862-47-0
• 化学式: C₃₄H₃₅FN₂O₅
• 分子量: 570.661
• InChiKey: RDXZJVLAFDSGAS-UHFFFAOYSA-N

物化性质

• 沸点：
  683.8±55.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 7-<2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-<(phenylamino)carbonyl>-1H-pyrrol-1-yl>-5-hydroxy-3-oxo-1-heptanoate 在 sodium hydroxide 、 sodium tetrahydroborate 、 三丁基硼 、 双氧水 作用下， 以 甲苯 为溶剂， 反应 9.0h， 生成 阿托伐他汀内酯
  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
• 作为产物：
  描述：

  ethyl α-bromo-4-fluorobenzeneacetate 在 盐酸 、 sodium hydroxide 、 正丁基锂 、 水 、 乙酸酐 、 sodium hydride 、 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 33.0h， 生成 methyl 7-<2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-<(phenylamino)carbonyl>-1H-pyrrol-1-yl>-5-hydroxy-3-oxo-1-heptanoate
  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-(3- or 4-Carboxamido-substituted pyrrol-1-yl)-alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0247633A1

  公开（公告）日：1987-12-02

  Certain trans-6-[2-(3- or 4-carboxamido-­substitutedpyrrol-1-yl)alkyl]-4-hydroxypyran-2-ones and the corresponding ring-opened acids derived therefrom which are potent inhibitors of the enzyme 3-hydroxy-3-­methylglutaryl-coenzyme A reductase (HMG CoA reductase) and are thus useful hypolipidemic or hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical composi­tions are also disclosed.

  特定的trans-6-[2-(3-或4-羧酰胺基取代吡咯-1-基)烷基]-4-羟基吡喃-2-酮及其相应的开环酸衍生物是酶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，因此可用作降脂或降胆固醇药物。还公开了含有这些化合物的制药组合物，以及使用这些制药组合物抑制胆固醇生物合成的方法。
• [EN] STABLE ORAL CI-981 FORMULATION AND PROCESS OF PREPARING SAME<br/>[FR] FORMULATION CI-981, ORALE, STABLE ET SON PROCEDE DE PREPARATION
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1994016693A1

  公开（公告）日：1994-08-04

  (EN) An oral pharmaceutical composition is provided for treating hypercholesterolemia or hyperlipidemia containing an advantageous formulation for stabilizing the HMG-CoA coenzyme A inhibitor, CI-981 Hemi-Calcium, of formula (IA) with effective amounts of calcium carbonate. A method for preparing a CI-981 stabilizing composition is described.(FR) Une composition pharmaceutique orale est utilisée dans le traitement de l'hypercholestérolémie ou l'hyperlipidémie et contient une formulation avantageuse permettant de stabiliser l'inhibiteur A coenzymatique HMG-CoA, l'Hemi-Calcium CI-981, de la formule (IA) avec des quantités efficaces de carbonate de calcium. L'invention concerne également un procédé de préparation d'une composition stabilisante CI-981.

  提供一种口服药物组合物，用于治疗高胆固醇血症或高脂血症，其中包含一种优越的配方，用于稳定式(I-A)的HMG-CoA辅酶A抑制剂CI-981 Hemi-Calcium，并含有有效量的碳酸钙。还描述了一种制备CI-981稳定组合物的方法。
• (R-(R*R*))-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl-3-phenyl-4((phenylamino)-carbonyl)-1H-pyrrole-1-heptanoic acid, its lactone form and salts thereof
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1061073A1

  公开（公告）日：2000-12-20

  [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-((1-methylethyl)-3-phenyl-4-[(phenylamino)-carbonyl)-1H-pyrrole-1-heptanoic acid or (2R-trans)-5-(4-fluorophenyl)-2-(1-methylethyl-N,4-diphenyl-1-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide; a process for their preparation and pharmaceutically acceptable salts thereof.

  [R-(R*,R*)]-2-(4-氟苯基)-β,δ-双羟基-5-((1-甲基乙基)-3-苯基-4-[(苯氨酰)基]-1H-吡咯-1-庚酸或(2R-trans)-5-(4-氟苯基)-2-(1-甲基乙基-N,4-二苯基-1-[2-(四氢-4-羟基-6-氧代-2H-吡喃-2-基)乙基]-1H-吡咯-3-羧酰胺；以及其制备方法和药学上可接受的盐。
• J. Med. Chem. 1991, 34, 357-366
  作者：

  DOI：——

  日期：——
• Drugs of the Future 1997, 22, 956
  作者：

  DOI：——

  日期：——