2-{[4-(2-Butynyloxy)phenyl]sulfinyl}-2-cyclohexyl-N-hydroxyacetamide | 287392-16-9

• 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: 2-{[4-(2-Butynyloxy)phenyl]sulfinyl}-2-cyclohexyl-N-hydroxyacetamide
• 英文别名: 2-{[4-(2-butynyl oxy)phenyl]sulfinyl}-2-cyclohexyl-N-hydroxyacetamide；2-(4-but-2-ynoxyphenyl)sulfinyl-2-cyclohexyl-N-hydroxyacetamide
• CAS: 287392-16-9
• 化学式: C₁₈H₂₃NO₄S
• 分子量: 349.451
• InChiKey: YAOLTEPPKVIFGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 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：
  94.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{[4-(2-Butynyloxy)phenyl]sulfinyl}-2-cyclohexyl-N-hydroxyacetamide 在 Oxone 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 6.0h， 以24%的产率得到2-{[4-(2-Butynyloxy)phenyl]sulfonyl}-2-cyclohexyl-N-hydroxyacetamide
  参考文献：
  名称：

  Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors

  摘要：

  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。

  公开号：

  US06340691B1
• 作为产物：
  描述：

  环己基乙酸 在 磷化氢 、 sodium hydroxide 、 草酰氯 、 硫酸 、 盐酸羟胺 、 双氧水 、 溴 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 氯仿 、 丙酮 、 乙腈 为溶剂， 反应 5.0h， 生成 2-{[4-(2-Butynyloxy)phenyl]sulfinyl}-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

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。
• [EN] TRIAZOLO[4,5-d] PYRIMIDINE DERIVATIVES AND THEIR USE AS PURINERGIC RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE TRIAZOLO[4,5-D] PYRIMIDINE ET LEUR UTILISATION EN TANT QU'AGONISTES DE RECEPTEUR PURINERGIQUE
  申请人：VERNALIS RES LTD

  公开号：WO2002055083A1

  公开（公告）日：2002-07-18

  The use of a compound of formula (I): wherein R1 is selected from H, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, halogen, CN, NR5R6, NR4COR5, NR4CONR5R6,NR4CO2R7 and NR4SO2R7; R2 is selected from aryl attached via an unsaturated carbon; R3 is selected from H, alkyl, COR5, CO2 R7, CONR5R6, CONR4NR5R6 and SO2R7; R4, R5 and R6 are independently selected from H, alkyl and aryl or where R5 and R6 are in an NR5R6 group, R5 and R6 may be linked to form a heterocyclic group, or where R4,R5 and R6 are in a (CONR4NR5R6) group, R4 and R5 may be linked to form a heterocyclic group; and R7 is selected from alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, in the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosine receptors and more particularly A2A receptors, may be beneficial, particularly wherein said disorder is a movement disorder such as Parkinson's disease or said disorder is depression, cognitive or memory impairment, acute or chronic pain, ADHD or narcolepsy, or for neuroprotection in a subject; compounds of formula (I) for use in therapy; and novel compounds of formula (I) per se.

  使用式(I)的化合物，其中R1从H，烷基，芳基，烷氧基，芳氧基，烷硫基，芳硫基，卤素，CN，NR5R6，NR4COR5，NR4CONR5R6，NR4CO2R7和NR4SO2R7中选择；R2从通过不饱和碳连接的芳基中选择；R3从H，烷基，COR5，CO2R7，CONR5R6，CONR4NR5R6和SO2R7中选择；R4，R5和R6独立地从H，烷基和芳基中选择，或者当R5和R6在NR5R6基团中时，R5和R6可以连接形成杂环基团，或者当R4，R5和R6在(CONR4NR5R6)基团中时，R4和R5可以连接形成杂环基团；R7从烷基和芳基中选择，或其药学上可接受的盐或前药，在治疗或预防阻断嘌呤受体，特别是腺苷受体，更具体地是A2A受体可能有益的疾病中使用，特别是其中所述疾病是运动障碍，如帕金森病，或所述疾病是抑郁症，认知或记忆障碍，急性或慢性疼痛，ADHD或嗜睡症，或用于保护神经系统。式(I)的化合物用于治疗；以及式(I)的新化合物本身。
• Method for the treatment of polycystic kidney disease
  申请人：——

  公开号：US20040063672A1

  公开（公告）日：2004-04-01

  The present invention provides a method for treating, inhibiting the progression of, or eradicating polycystic kidney disease of in a patient in need thereof which comprises providing to said patient an effective amount of a TACE inhibitor compound alone or in combination with an effective amount of an EDF receptor kinase inhibitor.

  本发明提供了一种治疗、抑制进展或根除多囊肾病的方法，该方法包括向需要该治疗的患者提供有效量的TACE抑制剂化合物，单独或与有效量的EDF受体激酶抑制剂化合物联合使用。
• Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and TACE inhibitors
  申请人：Wyeth Holdings Corporation

  公开号：US06825354B2

  公开（公告）日：2004-11-30

  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.

  该式化合物在治疗由TNF-α介导的疾病条件中很有用，例如类风湿性关节炎，骨关节炎，败血症，艾滋病，溃疡性结肠炎，多发性硬化症，克隆病和退行性软骨损失。
• 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