(11aS)-7-methoxy-8-(3-{4-[6-(4-methyl-1-piperazinyl)benzimidazol-2-yl]-phenoxy}propoxy)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one | 774221-56-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: (11aS)-7-methoxy-8-(3-{4-[6-(4-methyl-1-piperazinyl)benzimidazol-2-yl]-phenoxy}propoxy)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one
• 英文别名: (6aS)-2-methoxy-3-[3-[4-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]phenoxy]propoxy]-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-11-one
• CAS: 774221-56-6
• 化学式: C₃₄H₃₈N₆O₄
• 分子量: 594.714
• InChiKey: AQHPQTMEIVSAKL-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-(4-甲基哌嗪)-2-硝基苯胺 在 palladium on activated charcoal sodium metabisulfite 、 氢气 、 potassium carbonate 、 calcium carbonate 、 mercury dichloride 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 60.0h， 生成 (11aS)-7-methoxy-8-(3-{4-[6-(4-methyl-1-piperazinyl)benzimidazol-2-yl]-phenoxy}propoxy)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one
  参考文献：
  名称：

  Synthesis of C8-linked pyrrolo[2,1-c][1,4]benzodiazepine–benzimidazole conjugates with remarkable DNA-binding affinity

  摘要：

  Two types of benzimidazoles have been synthesized and linked to DC-81 at C8-position through different alkyl chain spacers. These PBD conjugates have exhibited remarkable DNA-binding affinity, and a representative compound shows promising in vitro anticancer activity. (C) 2004 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2004.06.069

文献信息

• [EN] PROCESS FOR PREPARING PYRROLO[2, 1-c] [1, 4] BENZODIAZEPINE HYBRIDS<br/>[FR] PROCEDE SERVANT A PREPARER DES HYBRIDES DE PYRROLO[2, 1-C] [1, 4] BENZODIAZEPINE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2005063759A1

  公开（公告）日：2005-07-14

  Novel pyrrolo[2, 1-c] [1, 4] benzodiazepine hybrids as well as processes for the proepartion of novel pyrrolo [2, 1-c] [1, 4] benzodiazepine hybrids are disclosed. More particularly, present invention relates to a process for the preparation of novel pyrrolo [2, 1-c] [1, 4] benzodiazepine hybrids as DNA sequence selective agents which are useful as potential antitumour agents. In particular, the present invention relates to a process for the preparation of new pyrrolo [2, 1-c] [1, 4] benzodiazepine hybrids as potential antitumour agents. These compounds have the formula (XIV).

  揭示了新型吡咯并[2,1-c][1,4]苯二氮䓬杂合物以及制备新型吡咯并[2,1-c][1,4]苯二氮䓬杂合物的方法。更具体地说，本发明涉及一种制备新型吡咯并[2,1-c][1,4]苯二氮䓬杂合物的方法，作为DNA序列选择性剂，可用作潜在的抗肿瘤剂。特别是，本发明涉及一种制备新型吡咯并[2,1-c][1,4]苯二氮䓬杂合物作为潜在抗肿瘤剂的方法。这些化合物的化学式为（XIV）。
• PROCESS FOR PREPARING PYRROLO[2, 1-C] [1,4] BENZODIAZEPINE HYBRIDS
  申请人：Kamal Ahmed

  公开号：US20050222133A1

  公开（公告）日：2005-10-06

  Novel pyrrolo[2,1-c][1,4]benzodiazepine hybrids as well as processes for the preparation of novel pyrrolo[2,1-c][1,4]benzodiazepine hybrids are dislcosed. More particularly, present invention relates to a process for the preparation of novel pyrrolo[2,1-c][1,4]benzodiazepine hybrids as DNA sequence selective agents which are useful as potential antitumour agents. In particular, the present invention relates to a process for the preparation of new pyrrolo [2,1-c][1,4]benzodiazepine hybrids as potential antitumour agents. These compounds have the formula XIV shown below:

  揭示了新型吡咯并[2,1-c][1,4]苯二氮杂环己烷杂合物以及制备新型吡咯并[2,1-c][1,4]苯二氮杂环己烷杂合物的方法。更具体地，本发明涉及一种制备新型吡咯并[2,1-c][1,4]苯二氮杂环己烷杂合物的方法，这些杂合物作为DNA序列选择性试剂，可用作潜在的抗肿瘤剂。特别是，本发明涉及一种制备新型吡咯并[2,1-c][1,4]苯二氮杂环己烷杂合物作为潜在抗肿瘤剂的方法。这些化合物的化学式如下所示：
• Spectroscopic and calorimetric studies on the DNA recognition of pyrrolo[2,1-c][1,4]benzodiazepine hybrids
  作者：Michael Rettig、Ahmed Kamal、R. Ramu、Judith Mikolajczak、Klaus Weisz

  DOI：10.1016/j.bmc.2008.11.033

  日期：2009.1

  of DNA melting temperatures by up to 40 °C for duplexes that allow for a covalent attachment of the PBD moiety to guanine bases in their minor groove. CD spectroscopic measurements suggest that the naphthalimide moiety of the drug interacts through intercalation. In contrast, the PBD-benzimidazole hybrid binds in the DNA minor groove with a preference for (A,T)4G sequences. Whereas the binding of both

  通过DNA熔解实验，紫外和荧光滴定法研究了由烷基化吡咯并[2,1- c ] [1,4]苯并二氮杂（PBD）部分束缚到萘二甲酰亚胺或苯基苯并咪唑发色团上的两个杂合配体的DNA结合， CD光谱和等温滴定热法（ITC）。两种杂合体的结合均导致了显着的热稳定性，双链体将DNA熔解温度提高了40°C，从而使PBD部分共价结合至其小沟中的鸟嘌呤碱基。CD光谱测量表明该药物的萘二甲酰亚胺部分通过嵌入相互作用。相反，PBD-苯并咪唑杂合体在DNA小沟中结合，优先选择（A，T）4G序列。尽管两个配体的结合都是焓驱动的并且与负熵相关，但与萘二甲酰亚胺混合体相比，苯并咪唑杂化体显示出较差的结合焓，该结合焓被更有利的熵项所抵消。