4-Methyl-3-oxo-2-[1-pyridin-2-yl-meth-(Z)-ylidene]-pentanoic acid methyl ester | 115672-61-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 4-Methyl-3-oxo-2-[1-pyridin-2-yl-meth-(Z)-ylidene]-pentanoic acid methyl ester
• 英文别名: 2-(2-Methyl-1-oxopropyl)-3-(2-pyridinyl)propenoic acid, methyl ester；methyl 4-methyl-3-oxo-2-(pyridin-2-ylmethylidene)pentanoate
• CAS: 115672-61-2
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: ZNASMOKHBQNQJT-UHFFFAOYSA-N

物化性质

• 沸点：
  349.0±27.0 °C(predicted)
• 密度：
  1.127±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Methyl-3-oxo-2-[1-pyridin-2-yl-meth-(Z)-ylidene]-pentanoic acid methyl ester 在 sodium hydroxide 、 2-(2-hydroxyethyl)-3-methyl-4-benzylthiazolium chloride 、 oxonium 、 水 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 48.0h， 生成 (4R,6R)-6-{2-[2-(4-Fluoro-phenyl)-5-isopropyl-3-pyridin-2-yl-pyrrol-1-yl]-ethyl}-4-hydroxy-tetrahydro-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
• 作为产物：
  描述：

  吡啶-2-甲醛 、 异丁酰醋酸甲酯 在 哌啶 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 4-Methyl-3-oxo-2-[1-pyridin-2-yl-meth-(Z)-ylidene]-pentanoic acid methyl 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

• Trans-6-[2-[2-(substituted-phenyl)-3- (or 4-)
  申请人：Warner-Lambert Company

  公开号：US04735958A1

  公开（公告）日：1988-04-05

  Certain trans-6-[2-[2-(substituted-phenyl)-3- (or 4-)heteroaryl-5-substituted-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-p yran-2-ones and the corresponding lactone-ring-opened acids 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.

  某些trans-6-[2-[2-(取代苯基)-3-(或4-)杂环芳基-5-取代-1H-吡咯-1-基]乙基]四氢-4-羟基-2H-吡喃-2-酮及其相应的开环酸是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，因此是有用的降脂或降胆固醇剂。还公开了含有这些化合物的药物组合物以及使用这些药物组合物抑制胆固醇生物合成的方法。