Tert-butyl 1-(1-chloroethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carboxylate | 330206-88-7

• 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: Tert-butyl 1-(1-chloroethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carboxylate
• CAS: 330206-88-7
• 化学式: C₁₉H₂₂ClNO₃
• 分子量: 347.842
• InChiKey: NGNZFLPSJXXEBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl 1-(1-chloroethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carboxylate 在 4 A molecular sieve 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成
  参考文献：
  名称：

  抗肿瘤药：开发用于选择性癌症治疗的强效糖苷类杜卡霉素类似物。

  摘要：

  DOI：

  10.1002/anie.200600936
• 作为产物：
  描述：

  5-benzyloxy-3-(tert.-butoxycarbonyl)-1-(1'-chloroethyl)-1,2-dihydro-3H-benzo[e]indole 在 palladium on activated charcoal 甲酸铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 Tert-butyl 1-(1-chloroethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carboxylate
  参考文献：
  名称：

  抗肿瘤药：开发用于选择性癌症治疗的强效糖苷类杜卡霉素类似物。

  摘要：

  DOI：

  10.1002/anie.200600936

文献信息

• Water-Soluble CC-1065 Analogs and Their Conjugates
  申请人：Beusker Patrick Henry

  公开号：US20090318668A1

  公开（公告）日：2009-12-24

  This invention relates to novel analogs of the DNA-binding alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

  这项发明涉及DNA结合烷基化剂CC-1065的新型类似物及其结合物。此外，该发明涉及用于制备上述剂和它们的结合物的中间体。这些结合物设计为在一个或多个激活步骤之后以及/或由结合物控制的速率和时间跨度下释放它们的（多种）荷载，以便选择性地传递和/或可控地释放一个或多个所述的DNA烷基化剂。这些剂、结合物和中间体可用于治疗以不良（细胞）增殖为特征的疾病。例如，这项发明的剂和结合物可用于治疗肿瘤。
• Novel prodrugs von 6-hydroxy-2,3-dihydro-1h-indoles, 5-hydroxy-1,2-dihydro-3h-pyrrolo[3,2-e]indoles and 5-hydroxy-1,2-dihydro-3h-benzo(e)indoles as well as of 6-hydroxy-1,2,3,4-tetrahydro-benzo[f]quinoline derivatives for use in selective cancer therapy
  申请人：——

  公开号：US20040033962A1

  公开（公告）日：2004-02-19

  The chemotherapy of malignant tumours is greatly restricted by the generally slight differentiation of the available cytostatic agents between normal and malignant tissue. In order to achieve an improvement of the selectivity in cancer therapy, novel prodrugs have been developed from 6-hydroxy-2,3-dihydro-1H-indolene, 5-hydroxy-1,2-dihydro-3H-pyrrolo[3,2-e]indolene and 5-hydroxy-1,2-dihydro-3H-benzo[e]indolene as well as from 6-hydroxy-1,2,3,4-tetrahydro-benzo[f]-quinolines, that may be used within the framework of the ADEP therapy (antibody directed enzyme prodrug therapy). The new prodrugs are characterised by a high difference in toxicity between the prodrug and underlying drug and by a very high efficacy of the drug. The high selectivity of the new prodrugs is probably attributed to the fact that, in the new prodrugs, a secondary halide is present in contrast to the prodrugs of a similar type previously produced by us. The direct alkylation of the DNA or RNA by the prodrugs and thus the toxicity of the prodrugs is thereby reduced. After splitting off of the glycosidic and/or acetal group on the phenolic hydroxy groups of the prodrugs, a spirocyclopropacyclohexadiene is formed which, being a highly toxic group, effects an alkylation of the DNA or RNA.

  恶性肿瘤的化疗受到限制，因为现有的细胞毒药物在正常组织和恶性组织之间的细胞毒作用差异很小。为了提高癌症治疗的选择性，从6-羟基-2,3-二氢-1H-吲哚烯、5-羟基-1,2-二氢-3H-吡咯[3,2-e]吲哚烯、5-羟基-1,2-二氢-3H-苯并[e]吲哚烯以及6-羟基-1,2,3,4-四氢-苯并[f]-喹啉中开发了新的前药，可在ADEP疗法（抗体导向酶前药疗法）框架内使用。新的前药具有前药和基础药物之间毒性差异很大以及药物非常高效的特点。新前药的高选择性可能归因于新前药中存在次卤化物，与我们之前生产的类似类型前药不同。前药直接烷基化DNA或RNA，从而减少了前药的毒性。在前药的酚羟基上脱去糖苷和/或缩醛基团后，形成了一个高毒性的螺环丙烷环己二烯，该基团对DNA或RNA进行烷基化。
• WO2007/89149
  申请人：——

  公开号：——

  公开（公告）日：——
• NEUE PRODRUGS VON 6-HYDROXY-2,3-DIHYDRO-1H-INDOLEN, 5-HYDROXY-1,2-DIHYDRO-3H-PYRROLO 3,2-E]INDOLEN UND 5-HYDROXY-1,2-DIHYDRO-3H-BENZO E]INDOLEN SOWIE VON 6-HYDROXY-1,2,3,4-TETRAHYDRO-BENZO F]CHINOLIN-DERIVATEN FÜR EINE SELEKTIVE KREBSTHERAPIE
  申请人：Tietze, Lutz F., Prof. Dr.

  公开号：EP1280771A2

  公开（公告）日：2003-02-05
• WATER-SOLUBLE CC-1065 ANALOGS AND THEIR CONJUGATES
  申请人：Syntarga B.V.

  公开号：EP1994000B1

  公开（公告）日：2017-08-23