(2-{2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxyphenylsulfanyl)-1-methylethylsulfanyl]phenoxy}acetylamino)acetic acid ethyl ester | 216168-60-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2-{2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxyphenylsulfanyl)-1-methylethylsulfanyl]phenoxy}acetylamino)acetic acid ethyl ester
• 英文别名: Ethyl 2-[[2-[2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenoxy]acetyl]amino]acetate；ethyl 2-[[2-[2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenoxy]acetyl]amino]acetate
• CAS: 216168-60-4
• 化学式: C₃₇H₅₇NO₅S₂
• 分子量: 659.995
• InChiKey: VMJSBACJHXYQTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  45
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-{2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxyphenylsulfanyl)-1-methylethylsulfanyl]phenoxy}acetylamino)acetic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以45%的产率得到glycine, N-[[4-[[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]thio]-2,6-bis(1,1-dimethylethyl)phenoxy]acetyl]-
  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 aluminum oxide 、 potassium fluoride 4-二甲氨基吡啶 、 lithium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (2-{2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxyphenylsulfanyl)-1-methylethylsulfanyl]phenoxy}acetylamino)acetic acid ethyl ester
  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

• Phenolic antioxidants for the treatment of disorders including arthritis, asthma and coronary artery disease
  申请人：Meng Q. Charles

  公开号：US20060020038A1

  公开（公告）日：2006-01-26

  The invention relates to compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds, wherein the compounds are of the following Formulas: or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein the substituents are defined in the application. The invention further provides methods of treatment of inflammatory disorders by administering the compounds.

  本发明涉及化合物、包含该化合物的药物组成物以及使用该化合物的方法，其中该化合物的结构式为：或其药学上可接受的盐、酯或前药，其中取代基在申请中有定义。本发明进一步提供通过给予该化合物治疗炎症性疾病的方法。
• [EN] PHENOLIC ANTIOXIDANTS FOR THE TREATMENT OF DISORDERS INCLUDING ARTHRITIS, ASTHMA AND CORONARY ARTERY DISEASE<br/>[FR] ANTIOXYDANTS PHÉNOLIQUES POUR LE TRAITEMENT DE TROUBLES INCLUANT L'ARTHRITE, L'ASTHME ET LES TROUBLES DES ARTÈRES CORONAIRES
  申请人：ATHEROGENICS INC

  公开号：WO2005112914A3

  公开（公告）日：2006-01-12
• US7271274B2
  申请人：——

  公开号：US7271274B2

  公开（公告）日：2007-09-18
• Discovery of Novel Phenolic Antioxidants as Inhibitors of Vascular Cell Adhesion Molecule-1 Expression for Use in Chronic Inflammatory Diseases
  作者：Charles Q. Meng、Patricia K. Somers、Lee K. Hoong、X. Sharon Zheng、Zhihong Ye、Kimberly J. Worsencroft、Jacob E. Simpson、Martha R. Hotema、M. David Weingarten、Mathew L. MacDonald、Russell R. Hill、Elaine M. Marino、Ki-Ling Suen、Jayraz Luchoomun、Charles Kunsch、Laura K. Landers、Dimitria Stefanopoulos、Randy B. Howard、Cynthia L. Sundell、Uday Saxena、Martin A. Wasserman、James A. Sikorski

  DOI：10.1021/jm049685u

  日期：2004.12.1

  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.