{[4-(2-butynyloxy)phenyl]sulfanyl}(cyclohexyl)acetic acid | 287393-02-6

• 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}(cyclohexyl)acetic acid
• 英文别名: ethyl {[4-(2-butynyloxy)phenyl]sulfanyl}(cyclohexyl)acetic acid；{[4-(2-butynyloxy)phenyl]sulfanyl}(cyclohexyl) acetic acid；2-(4-But-2-ynoxyphenyl)sulfanyl-2-cyclohexylacetic acid
• CAS: 287393-02-6
• 化学式: C₁₈H₂₂O₃S
• 分子量: 318.437
• InChiKey: BKQBPJYFKKYCAB-UHFFFAOYSA-N

物化性质

• 沸点：
  503.7±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {[4-(2-butynyloxy)phenyl]sulfanyl}(cyclohexyl)acetic acid 在 Oxone 、 草酰氯 、 盐酸羟胺 、 双氧水 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 6.0h， 生成 2-{[4-(2-Butynyloxy)phenyl]sulfonyl}-2-cyclohexyl-N-hydroxyacetamide
  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：

  环己基乙酸 在 磷化氢 、 sodium hydroxide 、 硫酸 、 溴 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 氯仿 、 丙酮 为溶剂， 反应 5.0h， 生成 {[4-(2-butynyloxy)phenyl]sulfanyl}(cyclohexyl)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
• [EN] ALKYNYL CONTAINING HYDROXAMIC ACID COMPOUNDS AS TACE INHIBITORS<br/>[FR] COMPOSES D'ACIDE HYDROXAMIQUE CONTENANT UN ALCYNYLE COMME INHIBITEURS D'ENZYME TACE
  申请人：AMERICAN CYANAMID CO

  公开号：WO2000044713A1

  公开（公告）日：2000-08-03

  The invention concerns compounds of formula (I) which are useful in treating disease conditions mediated by TNF-α, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.