3-[5-(1-propynyl)indole-2-carbonyl]-1-(S)-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole | 647022-05-7

• 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: 3-[5-(1-propynyl)indole-2-carbonyl]-1-(S)-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole
• 英文别名: [(1S)-1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indol-3-yl]-(5-prop-1-ynyl-1H-indol-2-yl)methanone
• CAS: 647022-05-7
• 化学式: C₂₅H₁₉ClN₂O₂
• 分子量: 414.891
• InChiKey: DJWLUSAEJYEPLY-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  56.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[5-(1-propynyl)indole-2-carbonyl]-1-(S)-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 CH₃CN 为溶剂， 反应 1.0h， 以79%的产率得到N2-{5-[1-(propynyl)indole-2-yl]carbonyl}-(8bR,9aS)-1,2,9,9a-tetrahydrocyclopropa[c]-benz[e]indol-4-one
  参考文献：
  名称：

  CBI analogues of the duocarmycins and CC-1065

  摘要：

  一系列广泛的CBI类似物，包括二聚卡蜜素和CC-1065的类似物，探索了第一个吲哚DNA结合亚基中取代基效应的细节。一般来说，在吲哚C5位置的取代导致细胞毒性增强，可以达到≧1000倍，提供了更强效（IC50=2-3 pM）的含有单个DNA结合亚基的简化类似物，比CBI-TMI、二聚卡蜜素SA或CC-1065更有效。细胞毒性增加与DNA烷基化速率和效率的增加密切相关。与基于DSA或CPI的类似物相比，这种效应在CBI类似物中更为显著。此外，这种效应对于C5取代基的电子性质不太敏感，但对于取代基的大小、刚性长度和形状（sp、sp2、sp3杂化）敏感，这与预期一致，即这种影响仅仅是由于其存在。

  公开号：

  US20050026987A1
• 作为产物：
  描述：

  (S)-1-(氯甲基)-5-羟基-1,2-二氢-3H-苯并[e]吲哚-3-羧酸叔丁酯 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 3-[5-(1-propynyl)indole-2-carbonyl]-1-(S)-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole
  参考文献：
  名称：

  Establishment of substituent effects in the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065

  摘要：

  An extensive series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be greater than or equal to 1000- fold providing simplified analogues containing a single DNA binding subunit that are more potent (IC50 = 2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00194-9

文献信息

• [EN] CBI ANALOGUES OF THE DUOCARMYCINS AND CC-1065<br/>[FR] ANALOGUES CBI DES DUOCARMYCINES ET DE CC-1065
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2004101767A2

  公开（公告）日：2004-11-25

  An extensive series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit is detailed. In general, substitution at the indole C5 position led to cytotoxic potency enhancements that can be ≥ 1000-fold providing simplified analogues containing a single DNA binding subunit that are more potent (IC50 = 2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065. The increases in cytotoxicity correlate well with accompanying increases in the rate and efficiency of DNA alkylation. This effect is more pronounced with the CBI versus DSA or CPI based analogues. Moreover, this effect is largely insensitive to the electronic character of the C5 substituent but is sensitive to the size, rigid length, and shape (sp, sp2, sp3 hybridization) of this substituent consistent with expectation that the impact is due simply to its presence.