5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-indole-2-carbonyl chloride | 593280-47-8

• 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: 5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-indole-2-carbonyl chloride
• CAS: 593280-47-8
• 化学式: C₂₀H₁₈Cl₃N₃O₂
• 分子量: 438.741
• InChiKey: IFMWAKXOBLPARB-UHFFFAOYSA-N

物化性质

• 沸点：
  581.6±50.0 °C(Predicted)
• 密度：
  1.457±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  28.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  65.2
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-amino-N-(5-{[(3-amino-3-iminopropyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide dihydrochloride 、 5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-indole-2-carbonyl chloride 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 20.0h， 以77%的产率得到3-[1-methyl-4[1-methyl-4[5-[4-N,N-bis(2-chloroethyl)aminobenzene-1-carboxamido]indole-2-carboxamido]-pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine hydrochloride
  参考文献：
  名称：

  Benzoyl and cinnamoyl nitrogen mustard derivatives of benzoheterocyclic analogues of the tallimustine: synthesis and antitumour activity

  摘要：

  A series of benzoyl and cinnamoyl nitrogen mustards tethered to different benzoheterocycles and to oligopyrroles structurally related to netropsin consisting of two pyrrole-amide units and terminating with an amidine moiety have been synthesised and a structure-activity relationship determined. Derivatives 3-10 have been evaluated for their sequence selective alkylating properties and cytotoxicity against human K562 leukaemia cells. They are 2- to 50-fold less cytotoxic than tallimustine, with compound 8 being the most potent member of this series. Among tallimustine isosters, the compounds with an indole 3 or benzothiophene 6 are 4-fold less cytotoxic than tallimustine, while the compounds with an N-methyl indole or benzofuran showed a 7- and 14-fold reduced cytotoxic potency, respectively. Our preliminary results indicate that these derivatives preferentially bind to AT-rich sequence with a sequence selectivity similar to tallimustine. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00425-4
• 作为产物：
  描述：

  5-[[4-[bis(2-chloroethyl)amino]benzoyl]amino]-1H-indole-2-carboxylic acid 在 氯化亚砜 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 5-{4-[Bis-(2-chloro-ethyl)-amino]-benzoylamino}-1H-indole-2-carbonyl chloride
  参考文献：
  名称：

  Benzoyl and cinnamoyl nitrogen mustard derivatives of benzoheterocyclic analogues of the tallimustine: synthesis and antitumour activity

  摘要：

  A series of benzoyl and cinnamoyl nitrogen mustards tethered to different benzoheterocycles and to oligopyrroles structurally related to netropsin consisting of two pyrrole-amide units and terminating with an amidine moiety have been synthesised and a structure-activity relationship determined. Derivatives 3-10 have been evaluated for their sequence selective alkylating properties and cytotoxicity against human K562 leukaemia cells. They are 2- to 50-fold less cytotoxic than tallimustine, with compound 8 being the most potent member of this series. Among tallimustine isosters, the compounds with an indole 3 or benzothiophene 6 are 4-fold less cytotoxic than tallimustine, while the compounds with an N-methyl indole or benzofuran showed a 7- and 14-fold reduced cytotoxic potency, respectively. Our preliminary results indicate that these derivatives preferentially bind to AT-rich sequence with a sequence selectivity similar to tallimustine. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00425-4

文献信息

• Benzoyl nitrogen mustard derivatives of benzoheterocyclic analogues of netropsin: Synthesis and biological activity
  作者：Pier Giovanni Baraldi、Romeo Romagnoli、Nicoletta Bianchi、Roberto Gambari

  DOI：10.1016/s0968-0896(03)00144-5

  日期：2003.5.29

  Synthesis, DNA binding properties and biological activity of a series of bis-benzoheterocycle derivatives 5-11, structurally related to the natural dipyrrole antitumor agent netropsin, and tethered to a benzoyl nitrogen mustard (BAM) as alkylating moiety is reported and structure-activity relationships determined. These compounds 5-11 have been evaluated for sequence selective alkylating properties

  报道了一系列与天然双吡咯抗肿瘤剂netropsin相关的双联苯并杂环衍生物5-11的合成，DNA结合特性和生物学活性，并报道了作为烷基化部分的苯甲酰氮芥（BAM）的结构和活性关系决心。已经评估了这些化合物5-11的序列选择性烷基化性质和对鼠L1210和人K562白血病细胞的细胞毒性。使用1型人类免疫缺陷病毒的长末端重复序列的一部分作为靶序列，我们发现这些化合物可诱导类似的DNA片段化模式。另外，获得的结果表明，所有合成的化合物在亚微摩尔范围内都保留了良好的抗增殖活性，并且通常比K562细胞对L1210更具活性。对于这两种细胞系，化合物6、7、10和11的效力最高，范围为0.3至1 microM，而化合物8和9的活性最低（IC（50）= 2-12 microM）。在化合物5-11中，发现衍生物11是此类化合物中最有效的成员，并且其抗K562和L1210细胞的活性分别比双吡咯对应物2低5和10