methyl(3S)-4-{[4-({7-[(tert-butoxycarbonyl)amino]-2-heptynyl}oxy)phenyl]sulfonyl}-2,2-dimethyl-3-thiomorpholine carboxylate | 287408-25-7

• 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: methyl(3S)-4-{[4-({7-[(tert-butoxycarbonyl)amino]-2-heptynyl}oxy)phenyl]sulfonyl}-2,2-dimethyl-3-thiomorpholine carboxylate
• 英文别名: methyl (3S)-2,2-dimethyl-4-[4-[7-[(2-methylpropan-2-yl)oxycarbonylamino]hept-2-ynoxy]phenyl]sulfonylthiomorpholine-3-carboxylate
• CAS: 287408-25-7
• 化学式: C₂₆H₃₈N₂O₇S₂
• 分子量: 554.729
• InChiKey: ADDQPUSFSGTXAR-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  145
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl(3S)-4-{[4-({7-[(tert-butoxycarbonyl)amino]-2-heptynyl}oxy)phenyl]sulfonyl}-2,2-dimethyl-3-thiomorpholine carboxylate 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 lithium iodide 作用下， 生成 (S)-tert-butyl 7-(4-(3-(hydroxycarbamoyl)-2,2-dimethylthiomorpholinosulfonyl)phenoxy)hept-5-ynylcarbamate
  参考文献：
  名称：

  Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates

  摘要：

  A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.

  DOI：

  10.1016/j.bmcl.2005.12.020
• 作为产物：
  描述：

  7-(tetrahydro-2H-pyran-2-yloxy)hept-2-yn-1-ol 在 sodium azide 、 四溴化碳 、 三丁基膦 、 水 、 4-甲基苯磺酸吡啶 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 methyl(3S)-4-{[4-({7-[(tert-butoxycarbonyl)amino]-2-heptynyl}oxy)phenyl]sulfonyl}-2,2-dimethyl-3-thiomorpholine carboxylate
  参考文献：
  名称：

  Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates

  摘要：

  A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.

  DOI：

  10.1016/j.bmcl.2005.12.020

文献信息

• Acetylenic alpha -amino acid-based sulfonamide hydroxamic acid tace inhibitors
  申请人：——

  公开号：US20030008849A1

  公开（公告）日：2003-01-09

  Compounds of the formula: 1 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.

  公式为1的化合物可用于治疗由TNF-&agr;介导的疾病条件，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、克罗恩病和退行性软骨丢失。
• Acetylenic alpha-amino acid-based sulfonamide hydroxamic acid tace inhibitors
  申请人：Levin I. Jeremy

  公开号：US20050113346A1

  公开（公告）日：2005-05-26

  Compounds of the formula: 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.

  式为的化合物在治疗由TNF-α介导的疾病条件方面非常有用，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、克罗恩病和退行性软骨损失。
• Acetylenic &agr;-amino acid-based sulfonamide hydroxamic acid tace inhibitors
  申请人：Wyeth Holdings Corporation

  公开号：US06812227B2

  公开（公告）日：2004-11-02

  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.

  公式为的化合物在治疗由TNF-α介导的疾病状况中是有用的，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、克罗恩病和软骨退化损失。
• US6716833B2
  申请人：——

  公开号：US6716833B2

  公开（公告）日：2004-04-06
• Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates
  作者：J.I. Levin、J.M. Chen、L.M. Laakso、M. Du、J. Schmid、W. Xu、T. Cummons、J. Xu、G. Jin、D. Barone、J.S. Skotnicki

  DOI：10.1016/j.bmcl.2005.12.020

  日期：2006.3

  A series of thiomorpholine sulfonamide hydroxamate TACE inhibitors, all bearing propargylic ether P1' groups, was explored. In particular, compound 5h has excellent in vitro potency against isolated TACE enzyme and in cells, oral activity in a model of TNF-alpha production and a collagen-induced arthritis model, was selected as a clinical candidate for the treatment of RA.