{[4-(2-butynyloxy)phenyl]sulfanyl}(4-methoxyphenyl)acetic acid | 287393-05-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: {[4-(2-butynyloxy)phenyl]sulfanyl}(4-methoxyphenyl)acetic acid
• 英文别名: {[4-(2-butynyloxy)phenyl]sulfanyl}(4-methoxyphenyl) acetic acid；{[4-(2-bytynyloxy)phenyl]sulfanyl}(4-methoxyphenyl) acetic acid；2-(4-but-2-ynoxyphenyl)sulfanyl-2-(4-methoxyphenyl)acetic acid
• CAS: 287393-05-9
• 化学式: C₁₉H₁₈O₄S
• 分子量: 342.416
• InChiKey: RWQSUCDFUCUAOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {[4-(2-butynyloxy)phenyl]sulfanyl}(4-methoxyphenyl)acetic acid 在 草酰氯 、 盐酸羟胺 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-{[4-(2-Butynyloxy)phenyl]sulfanyl}-N-hydroxy-2-(4-methoxyphenyl) acetamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors

  摘要：

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.

  DOI：

  10.1021/jm040086x
• 作为产物：
  描述：

  ethyl [4-(hydroxyphenyl)sulfanyl](4-methoxyphenyl)acetate 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 生成 {[4-(2-butynyloxy)phenyl]sulfanyl}(4-methoxyphenyl)acetic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors

  摘要：

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.

  DOI：

  10.1021/jm040086x

文献信息

• Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors
  申请人：American Cyanamid Company

  公开号：US06340691B1

  公开（公告）日：2002-01-22

  Compounds of the formula are useful in treating disease conditions mediated by TNF-&agr;, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.

  该公式的化合物可用于治疗由TNF-α介导的疾病状况，例如类风湿性关节炎、骨关节炎、脓毒症、艾滋病、溃疡性结肠炎、多发性硬化症、克罗恩病和退化性软骨丧失。
• ALKYNYL CONTAINING HYDROXAMIC ACID COMPOUNDS AS TACE INHIBITORS
  申请人：Wyeth Holdings Corporation

  公开号：EP1147080B1

  公开（公告）日：2004-07-21
• US6340691B1
  申请人：——

  公开号：US6340691B1

  公开（公告）日：2002-01-22
• US6825354B2
  申请人：——

  公开号：US6825354B2

  公开（公告）日：2004-11-30
• Synthesis and Structure−Activity Relationships of 4-alkynyloxy Phenyl Sulfanyl, Sulfinyl, and Sulfonyl Alkyl Hydroxamates as Tumor Necrosis Factor-α Converting Enzyme and Matrix Metalloproteinase Inhibitors
  作者：Aranapakam M. Venkatesan、Jamie M. Davis、George T. Grosu、Jannie Baker、Arie Zask、Jeremy I. Levin、John Ellingboe、Jerauld S. Skotnicki、John F. DiJoseph、Amy Sung、Guixian Jin、Weixin Xu、Diane Joseph McCarthy、Dauphine Barone

  DOI：10.1021/jm040086x

  日期：2004.12.1

  A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (NIMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested. The sulfinyl derivatives showed a preference for a specific oxidation on sulfur as in compounds 25-28. The selectivity over MMPs was also demonstrated in the sulfonyl series. The enhanced cellular activity was achieved upon incorporating a butynyloxy substituent in the piperidene series. Compounds 64 and 65 were potent inhibitors of TNF-alpha release in the mouse at 100 mg/kg po.