3-{(E)-6-[4-Chloro-2-(3,4-dimethyl-pyrrol-1-yl)-phenyl]-hex-5-enyl}-5-methoxycarbonylmethyl-4,5-dihydro-isoxazole-5-carboxylic acid methyl ester | 213541-80-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-{(E)-6-[4-Chloro-2-(3,4-dimethyl-pyrrol-1-yl)-phenyl]-hex-5-enyl}-5-methoxycarbonylmethyl-4,5-dihydro-isoxazole-5-carboxylic acid methyl ester
• 英文别名: methyl 3-[6-[4-chloro-2-(3,4-dimethylpyrrol-1-yl)phenyl]hex-5-enyl]-5-(2-methoxy-2-oxoethyl)-4H-1,2-oxazole-5-carboxylate
• CAS: 213541-80-1
• 化学式: C₂₆H₃₁ClN₂O₅
• 分子量: 486.996
• InChiKey: NEFVMMRUBCLYCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  34.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  79.12
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-{(E)-6-[4-Chloro-2-(3,4-dimethyl-pyrrol-1-yl)-phenyl]-hex-5-enyl}-5-methoxycarbonylmethyl-4,5-dihydro-isoxazole-5-carboxylic acid methyl ester 在 platinum(IV) oxide 、 Ra-Ni 氢气 、 硼酸 作用下， 以 甲醇 为溶剂， 反应 4.5h， 生成 Dimethyl 2-[8-[4-chloro-2-(3,4-dimethylpyrrol-1-yl)phenyl]-2-oxooctyl]-2-hydroxybutanedioate
  参考文献：
  名称：

  ATP-Citrate Lyase as a Target for Hypolipidemic Intervention. 2. Synthesis and Evaluation of (3R*,5S*)-ω-Substituted-3-carboxy-3,5-dihydroxyalkanoic Acids and Their γ-Lactone Prodrugs as Inhibitors of the Enzyme in Vitro and in Vivo

  摘要：

  series of (3R*,5S*)-omega-substituted-3-carboxy-3,5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have K-i's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.

  DOI：

  10.1021/jm980091z
• 作为产物：
  描述：

  6-Hydroxy-hexanal oxime 在 草酰氯 、 dimsylsodium 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.67h， 生成 3-{(E)-6-[4-Chloro-2-(3,4-dimethyl-pyrrol-1-yl)-phenyl]-hex-5-enyl}-5-methoxycarbonylmethyl-4,5-dihydro-isoxazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  ATP-Citrate Lyase as a Target for Hypolipidemic Intervention. 2. Synthesis and Evaluation of (3R*,5S*)-ω-Substituted-3-carboxy-3,5-dihydroxyalkanoic Acids and Their γ-Lactone Prodrugs as Inhibitors of the Enzyme in Vitro and in Vivo

  摘要：

  series of (3R*,5S*)-omega-substituted-3-carboxy-3,5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have K-i's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.

  DOI：

  10.1021/jm980091z