(+/-)5-(carbomethoxymethyl)-3-(5-hydroxypentyl)-5-methoxycarbonyl-4,5-dihydroisoxazole | 154566-36-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (+/-)5-(carbomethoxymethyl)-3-(5-hydroxypentyl)-5-methoxycarbonyl-4,5-dihydroisoxazole
• 英文别名: 5-(Carbomethoxymethyl)-3-(5-hydroxypentyl)-5-methoxycarbonyl-4,5-dihydroisoxazole；methyl 3-(5-hydroxypentyl)-5-(2-methoxy-2-oxoethyl)-4H-1,2-oxazole-5-carboxylate
• CAS: 154566-36-6
• 化学式: C₁₃H₂₁NO₆
• 分子量: 287.313
• InChiKey: YSMFMKMJXONUIU-UHFFFAOYSA-N

物化性质

• 沸点：
  386.0±52.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  94.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+/-)5-(carbomethoxymethyl)-3-(5-hydroxypentyl)-5-methoxycarbonyl-4,5-dihydroisoxazole 在 Ra-Ni sodium tetrahydroborate 、 氢气 、 硼酸 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成
  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：

  衣康酸二甲酯 、 6-Hydroxy-hexanal oxime 在 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 (+/-)5-(carbomethoxymethyl)-3-(5-hydroxypentyl)-5-methoxycarbonyl-4,5-dihydroisoxazole
  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

文献信息

• Phenylderivate as inhibitors of ATP citrate lyase
  申请人：SmithKline Beecham p.l.c.

  公开号：US05447954A1

  公开（公告）日：1995-09-05

  Compounds of the formula ##STR1## where the substituents are defined in the specification useful in the treatment of hyperlipidemia.

  式子为##STR1##的化合物，其中取代基在说明书中定义，可用于治疗高脂血症。
• [EN] PHENYLDERIVATE AS INHIBITORS OF ATP CITRATE LYASE<br/>[FR] DERIVE DE PHENYLE UTILISE COMME INHIBITEUR DE CITRATE LYASE D'ADENOSINE-TRIPHOSPHATE (ATP)
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1993022304A1

  公开（公告）日：1993-11-11

  (EN) Novel phenyl derivatives, processes for their preparation and their use as medicaments are disclosed.(FR) L'invention se rapporte à de nouveaux dérivés de phényle, à des processus de préparation de ces dérivés, et à leur utilisation comme médicaments.

  （中）本发明公开了新的苯基衍生物、制备这些衍生物的过程以及它们作为药物的用途。
• PHENYLDERIVATE AS INHIBITORS OF ATP CITRATE LYASE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0639187A1

  公开（公告）日：1995-02-22
• US5447954A
  申请人：——

  公开号：US5447954A

  公开（公告）日：1995-09-05
• ATP-Citrate Lyase as a Target for Hypolipidemic Intervention. 2. Synthesis and Evaluation of (3<i>R</i>*,5<i>S</i>*)-ω-Substituted-3-carboxy-3,5-dihydroxyalkanoic Acids and Their γ-Lactone Prodrugs as Inhibitors of the Enzyme in Vitro and in Vivo
  作者：Andrew D. Gribble、Robert J. Ife、Antony Shaw、David McNair、Christine E. Novelli、Susan Bakewell、Virendra P. Shah、Roland E. Dolle、Pieter H. Groot、Nigel Pearce、John Yates、David Tew、Helen Boyd、Stephen Ashman、Drake S. Eggleston、R. Curtis Haltiwanger、George Okafo

  DOI：10.1021/jm980091z

  日期：1998.9.1

  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.