2-((3R,5S)-5-(6-(2,4-二氯苯基)己基)-3-羟基-2-氧代四氢呋喃-3-基)乙酸 | 154566-12-8

• 物质功能分类: 生物化工 - 抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-((3R,5S)-5-(6-(2,4-二氯苯基)己基)-3-羟基-2-氧代四氢呋喃-3-基)乙酸
• 中文别名: (3R，5S)-rel-5-[6-(2,4-二氯苯基)己基]四氢-3-羟基-2-氧代-3-呋喃乙酸
• 英文名称: SB-204990
• 英文别名: (3R,5S)-rel-5-[6-(2,4-Dichlorophenyl)hexyl]tetrahydro-3-hydroxy-2-oxo-3-furanaceticacid；2-[(3S,5R)-5-[6-(2,4-dichlorophenyl)hexyl]-3-hydroxy-2-oxooxolan-3-yl]acetic acid
• CAS: 154566-12-8
• 化学式: C₁₈H₂₂Cl₂O₅
• 分子量: 389.276
• InChiKey: YTRNLFYTHYWDAU-KDOFPFPSSA-N

物化性质

• 熔点：
  87-89 °C
• 沸点：
  571.6±40.0 °C(Predicted)
• 密度：
  1.332±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL； DMF:PBS(pH7.2)(1:2)：0.33mg/ml； DMSO：20mg/mL；乙醇：1mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

SB 204990是ATP柠檬酸裂解酶（ACLY）的有效特异性抑制剂。

靶点

ACLY。

体外研究

SB204990（SB）是一种特定的ACLY酶抑制剂。SB204990处理会导致细胞质中乙酰辅酶A水平下降，从而预期减少可被乙酸化和活化的β-连环蛋白水平。

体内研究

当通过口服给予大鼠时，SB 204990会被系统循环吸收。在饮食中（0.05%-0.25%，按重量计）持续一周后，SB 204990导致大鼠血浆胆固醇水平呈剂量依赖性下降（最多减少46%），甘油三酯水平最多下降80%。同样地，在狗中以每天25 mg/kg的剂量给药时，SB 204990也降低了血浆胆固醇水平（最多降低23%）和甘油三酯水平（最多降低38%），并且更倾向于减少低密度脂蛋白胆固醇水平而非高密度脂蛋白胆固醇。

反应信息

• 作为反应物：
  描述：

  2-((3R,5S)-5-(6-(2,4-二氯苯基)己基)-3-羟基-2-氧代四氢呋喃-3-基)乙酸 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以100 mg的产率得到(3S,5R)-3-carboxy-11-(2,4-dichlorophenyl)-3,5-dihydroundecanoic acid disodium salt
  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：

  (+/-)methyl 11-(2,4-dichlorophenyl)-3-hydroxy-3-methoxycarbonyl-5-oxo-undecanoate 在 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 10.5h， 生成 2-((3R,5S)-5-(6-(2,4-二氯苯基)己基)-3-羟基-2-氧代四氢呋喃-3-基)乙酸
  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

• CHARACTERIZATION AND ANALYSIS OF THE COMPOSITION AND DYNAMICS OF THE MAMMALIAN RIBOPROTEOME
  申请人：Beth Israel Deaconess Medical Center, Inc.

  公开号：US20150079590A1

  公开（公告）日：2015-03-19

  The present invention relates to methods for identifying compounds that modulate the translation machinery and methods of diagnosing cancer related to deregulation of the translation machinery. In particular, the methods and diagnostic tests include determining an association between one or more targets and one or more components of the riboproteome and treating a subject with cancer by administering a compound that modulates the association between one or more targets and one or more components of the riboproteome.
• METHODS OF TREATING PROLIFERATIVE DISORDERS WITH MALATE OR DERIVATIVES THEREOF
  申请人：Sukhatme Vikas P.

  公开号：US20150056215A1

  公开（公告）日：2015-02-26

  The present invention relates to methods, compositions, and diagnostic tests for treating and diagnosing proliferative disorders, such as cancel-, that result in dysregulation of malic enzyme 2. In particular, the methods and compositions include monotherapy with malate, or a derivative thereof, as well as combination therapy, such as malate, or a derivative thereof, combined with another therapeutic agent, such as a malic enzyme 2 inhibitor, an antineoplastic agent, a glycolysis inhibitor, an antiangiogenic agent, an immunomodulatory agent, an antibody, or a cytokine.
• US9931313B2
  申请人：——

  公开号：US9931313B2

  公开（公告）日：2018-04-03
• [EN] METHODS OF TREATING PROLIFERATIVE DISORDERS WITH MALATE OR DERIVATIVES THEREOF<br/>[FR] PROCÉDÉS DE TRAITEMENT DE TROUBLES PROLIFÉRATIFS AVEC DU MALATE OU DES DÉRIVÉS DE CELUI-CI
  申请人：BETH ISRAEL HOSPITAL

  公开号：WO2013152193A2

  公开（公告）日：2013-10-10

  The present invention relates to methods, compositions, and diagnostic tests for treating and diagnosing proliferative disorders, such as cancel-, that result in dysregulation of malic enzyme 2. In particular, the methods and compositions include monotherapy with malate, or a derivative thereof, as well as combination therapy, such as malate, or a derivative thereof, combined with another therapeutic agent, such as a malic enzyme 2 inhibitor, an antineoplastic agent, a glycolysis inhibitor, an antiangiogenic agent, an immunomodulatory agent, an antibody, or a cytokine.
• 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.