5-[4-[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]-thio-2,6-bis(1,1-dimethylethyl)phenoxy]-2(R),3(R),4(R)-trihydroxy-pentanoic acid | 366494-61-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-[4-[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]-thio-2,6-bis(1,1-dimethylethyl)phenoxy]-2(R),3(R),4(R)-trihydroxy-pentanoic acid
• 英文别名: (2R,3R,4R)-5-[2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenoxy]-2,3,4-trihydroxypentanoic acid
• CAS: 366494-61-3
• 化学式: C₃₆H₅₆O₇S₂
• 分子量: 664.968
• InChiKey: UENJUUTXIMHHPK-CRXYYGHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  178
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-[4-[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]-thio-2,6-bis(1,1-dimethylethyl)phenoxy]-2(R),3(R),4(R)-trihydroxy-pentanoic acid 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以15%的产率得到(2S,3S,4R)-5-[2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenoxy]pentane-1,2,3,4-tetrol
  参考文献：
  名称：

  Discovery of Novel Phenolic Antioxidants as Inhibitors of Vascular Cell Adhesion Molecule-1 Expression for Use in Chronic Inflammatory Diseases

  摘要：

  Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelial cells and is implicated in many inflammatory conditions. Since part of the signal transduction pathway that regulates the activation of VCAM-1 expression is redox-sensitive, compounds with antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been designed and synthesized starting from probucol (1). Many of these compounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and displayed potent antioxidant effects in. vitro. Some of these derivatives (4o, 4p, 4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 from human peripheral blood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showed antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplant rejection, respectively.

  DOI：

  10.1021/jm049685u
• 作为产物：
  描述：

  普罗布考 在 sodium hydroxide 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 5-[4-[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]-thio-2,6-bis(1,1-dimethylethyl)phenoxy]-2(R),3(R),4(R)-trihydroxy-pentanoic acid
  参考文献：
  名称：

  Discovery of Novel Phenolic Antioxidants as Inhibitors of Vascular Cell Adhesion Molecule-1 Expression for Use in Chronic Inflammatory Diseases

  摘要：

  Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelial cells and is implicated in many inflammatory conditions. Since part of the signal transduction pathway that regulates the activation of VCAM-1 expression is redox-sensitive, compounds with antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been designed and synthesized starting from probucol (1). Many of these compounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and displayed potent antioxidant effects in. vitro. Some of these derivatives (4o, 4p, 4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 from human peripheral blood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showed antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplant rejection, respectively.

  DOI：

  10.1021/jm049685u

文献信息

• Compounds and methods to increase plasma HDL cholesterol levels and improve HDL functionality
  申请人：——

  公开号：US20020016364A1

  公开（公告）日：2002-02-07

  It has been discovered that certain selected ethers of probucol, and their pharmaceutically acceptable salts or prodrugs, are useful for increasing circulating HDL cholesterol. These compounds may also improve HDL functionality by (a) increasing clearance of cholesteryl esters, (b) increasing HDL-particle affinity for hepatic cell surface receptors or (c) increasing the half life of apoAI-HDL.

  已发现，普布考尔的某些选择性醚类化合物及其药用盐或前药对增加循环高密度脂蛋白胆固醇具有益处。这些化合物还可以通过以下方式改善高密度脂蛋白的功能：(a)增加胆固醇酯的清除，(b)增加高密度脂蛋白颗粒对肝细胞表面受体的亲和力，或者(c)增加apoAI-HDL的半衰期。
• COMPOUNDS AND METHODS TO INCREASE PLASMA HDL CHOLESTEROL LEVELS AND IMPROVE HDL FUNCTIONALITY
  申请人：Atherogenics, Inc.

  公开号：EP1272465A2

  公开（公告）日：2003-01-08
• US6881860B2
  申请人：——

  公开号：US6881860B2

  公开（公告）日：2005-04-19
• US7183317B2
  申请人：——

  公开号：US7183317B2

  公开（公告）日：2007-02-27
• [EN] COMPOUNDS AND METHODS TO INCREASE PLASMA HDL CHOLESTEROL LEVELS AND IMPROVE HDL FUNCTIONALITY<br/>[FR] COMPOSES ET PROCEDES DESTINES A ACCROITRE LES NIVEAUX PLASMATIQUES DE HDL CHOLESTEROL ET A AMELIORER LA FONCTIONNALITE DE HDL
  申请人：ATHEROGENICS INC

  公开号：WO2001077072A2

  公开（公告）日：2001-10-18

  It has been discovered that certain selected ethers of probucol, and their pharmaceutically acceptable salts or prodrugs, are useful for increasing circulating HDL cholesterol. These compounds may also improve HDL functionality by (a) increasing clearance of cholesteryl esters, (b) increasing HDL-particle affinity for hepatic cell surface receptors or (c) increasing the half life of apoAI-HDL.