methyl 3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylate | 404951-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylate
• 英文别名: 3-[4-({[2-(tert-butyldimethylsilanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-(2E)-2-propenoic acid methyl ester；methyl (E)-3-[4-[[2-[tert-butyl(dimethyl)silyl]oxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enoate
• CAS: 404951-56-0
• 化学式: C₂₉H₄₀N₂O₃Si
• 分子量: 492.734
• InChiKey: KGSIGGLFUJYHRA-FOCLMDBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.42
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylate 生成 N-hydroxy-3-[4-({[2-(tert-butyldimethylsilanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-(2E)-2-propenamide
  参考文献：
  名称：

  HYDROXAMATE DERIVATIVES USEFUL AS DEACETYLASE INHIBITORS

  摘要：

  公开号：

  EP1318980A2
• 作为产物：
  描述：

  （2-溴乙氧基）-特丁基二甲基硅烷 、 (2E)-3-[4-[[[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenoic acid methyl ester 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以97%的产率得到methyl 3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylate
  参考文献：
  名称：

  [EN] INHIBITORS OF HISTONE DEACETYLASE
  [FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE

  摘要：

  这项发明涉及一系列对抑制组蛋白去乙酰化酶（HDAC）酶活性有用的化合物。该发明还提供了一种利用这些化合物抑制细胞中组蛋白去乙酰化酶的方法，以及一种利用这些HDAC抑制剂治疗细胞增殖性疾病和病况的方法。此外，该发明提供了包含这些HDAC抑制化合物和药用可接受载体的药物组合物。

  公开号：

  WO2005092899A1

文献信息

• [EN] INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE
  申请人：METHYLGENE INC

  公开号：WO2005092899A1

  公开（公告）日：2005-10-06

  The invention relates to a series of compounds useful for inhibiting histone deacetylase (HDAC) enzymatic activity. The invention also provides a method for inhibiting histone descetylase in a cell using said compounds as well as a method for treating cell proliferative diseases and conditions using said HDAC inhibitors. Further, the invention provides pharmaceutical compositions comprising the HDAC inhibiting compounds and a pharmaceutically acceptable carrier.

  这项发明涉及一系列对抑制组蛋白去乙酰化酶（HDAC）酶活性有用的化合物。该发明还提供了一种利用这些化合物抑制细胞中组蛋白去乙酰化酶的方法，以及一种利用这些HDAC抑制剂治疗细胞增殖性疾病和病况的方法。此外，该发明提供了包含这些HDAC抑制化合物和药用可接受载体的药物组合物。
• Rapid method for screening compounds for in vivo activity
  申请人：——

  公开号：US20040067540A1

  公开（公告）日：2004-04-08

  The present invention provides a rapid method for screening potentially pharmaceutically useful compounds for activity in vivo. The method has the steps of growing a target cell into which a reporter gene was introduced in a biocompatible, semipermeable encapsulation device; implanting the semi-permeable encapsulation device into a subject; administering a potentially pharmaceutically active compound to said subject; removing said encapsulation device from said subject after in vivo exposure to the potentially pharmaceutically active compound and evaluating said target cell for reaction to said potentially paharmaceutically active compound by measuring the expression of said reporter gene.

  本发明提供了一种快速筛选潜在药用化合物在体内活性的方法。该方法包括以下步骤：将报告基因引入到一个靶细胞中，并将该细胞生长于一种生物相容的半透性封装装置中；将该半透性封装装置植入到一个受试者体内；向该受试者施用一种潜在药用活性化合物；在该潜在药用活性化合物在体内暴露后，将该封装装置从该受试者体内移除，并通过测量该报告基因的表达来评估该靶细胞对该潜在药用活性化合物的反应。
• Deacetylase inhibitors
  申请人：Remiszewski William Stacy

  公开号：US20050085507A1

  公开（公告）日：2005-04-21

  The present invention provides hydroxamate compounds which are deacetylase inhibitors. The compounds are suitable for pharmaceutical compositions having anti-proliferative properties.

  本发明提供了羟酰胺化合物，它们是去乙酰化酶抑制剂。这些化合物适用于具有抗增殖性能的药物组合物。
• Method for screening for compounds having hdac inhibitory activity
  申请人：Asselbergs Maria Fredericus Alphonsus

  公开号：US20050118596A1

  公开（公告）日：2005-06-02

  The invention relates to the use of Fra-1 levels as a marker for HDAC inhibition. Also disclosed are in vivo and in vitro methods for screening a compound for HDAC inhibitory activity, as well as methods for monitoring the therapeutic efficacy of an HDAC inhibitor in a subject in vivo and for determining resistance to an HDAC inhibitor in vitro or in vivo.

  本发明涉及使用Fra-1水平作为HDAC抑制剂的标记。还揭示了一种用于筛选具有HDAC抑制活性的化合物的体内和体外方法，以及用于监测体内HDAC抑制剂的治疗功效的方法，以及用于确定体外或体内对HDAC抑制剂的耐药性的方法。
• Cyclooxygenase-2 inhibitor/histone deacetylase inhibitor combination
  申请人：Chen Pan Ying-Nan

  公开号：US20050032899A1

  公开（公告）日：2005-02-10

  The invention relates to a combination which comprises (a) a cyclooxygenase-2 inhibitor (“COX-2 inhibitor”) and (b) a histone deacetylase inhibitor (“HDAI”) for simultaneous, concurrent, separate or sequential use, especially for use in the treatment of pre-malignant colon lesions or a colon cancer or other malignancies in a mammal, particularly a human. The invention also relates to pharmaceutical compositions comprising such a combination and to a method of treating pre-malignant colon lesions (e.g. polyps) and colon cancer, as well as other malignancies, in a mammal, particularly a human, with such a combination. The present invention further also relates to a commercial package or product comprising such a combination.

  本发明涉及一种组合物，包括(a)环氧合酶-2抑制剂（“COX-2抑制剂”）和(b)组蛋白去乙酰化酶抑制剂（“HDAI”），用于同时、并行、分离或顺序使用，特别是用于治疗哺乳动物，特别是人类的癌前结肠病变或结肠癌或其他恶性肿瘤。本发明还涉及包括这种组合物的制药组合物以及使用这种组合物治疗癌前结肠病变（例如息肉）和结肠癌以及其他恶性肿瘤的方法，特别是在哺乳动物，特别是人类中。本发明还涉及包含这种组合物的商业包装或产品。