[4-[4-[4-[4-[4-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidine-1-carbonyl]-2-methoxy-5-nitrophenoxy]butyl]piperazin-1-yl]butoxy]-5-methoxy-2-nitrophenyl]-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidin-1-yl]methanone | 1145663-19-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-[4-[4-[4-[4-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidine-1-carbonyl]-2-methoxy-5-nitrophenoxy]butyl]piperazin-1-yl]butoxy]-5-methoxy-2-nitrophenyl]-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidin-1-yl]methanone
• CAS: 1145663-19-9
• 化学式: C₄₆H₆₆F₄N₆O₁₀S₄
• 分子量: 1067.32
• InChiKey: YWJZAMBPBBOLMZ-ZPGRZCPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  70
• 可旋转键数：
  26
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  277
• 氢给体数：
  0
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  [4-[4-[4-[4-[4-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidine-1-carbonyl]-2-methoxy-5-nitrophenoxy]butyl]piperazin-1-yl]butoxy]-5-methoxy-2-nitrophenyl]-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidin-1-yl]methanone 在 甲醇 、 tin(II) chloride dihdyrate 、 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 生成 [2-amino-4-[4-[4-[4-[5-amino-4-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidine-1-carbonyl]-2-methoxyphenoxy]butyl]piperazin-1-yl]butoxy]-5-methoxyphenyl]-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidin-1-yl]methanone
  参考文献：
  名称：

  [EN] C2-FLUORO SUBSTITUTED PIPERAZINE LINKED PYRROLO[2,1-C][1,4] BENZODIAZEPINE DIMERS AND A PROCESS FOR THE PREPARATION THEREOF
  [FR] DIMÈRES DE PYRROLO[2,1-C][1,4] BENZODIAZÉPINE LIÉS UN CYCLE PIPÉRAZINE SUBSTITUÉS PAR C2-FLUORÉ ET SON PROCÉDÉ DE PRÉPARATION

  摘要：

  本发明提供了一种一般式IXa-d的化合物，可作为潜在的抗肿瘤剂，并且包含这些化合物的药物组合物在pH为7.00的水相磷酸钠缓冲液中与小牛胸腺（CT）DNA的摩尔比为1:5时表现出结合亲和力。本发明还提供了一种制备C2-氟取代哌嗪连接的吡咯[2,1c][1-4]，苯二氮䓬的配方（IX）的方法。

  公开号：

  WO2009113084A1
• 作为产物：
  描述：

  (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 96.0h， 生成 [4-[4-[4-[4-[4-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidine-1-carbonyl]-2-methoxy-5-nitrophenoxy]butyl]piperazin-1-yl]butoxy]-5-methoxy-2-nitrophenyl]-[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidin-1-yl]methanone
  参考文献：
  名称：

  [EN] C2-FLUORO SUBSTITUTED PIPERAZINE LINKED PYRROLO[2,1-C][1,4] BENZODIAZEPINE DIMERS AND A PROCESS FOR THE PREPARATION THEREOF
  [FR] DIMÈRES DE PYRROLO[2,1-C][1,4] BENZODIAZÉPINE LIÉS UN CYCLE PIPÉRAZINE SUBSTITUÉS PAR C2-FLUORÉ ET SON PROCÉDÉ DE PRÉPARATION

  摘要：

  本发明提供了一种一般式IXa-d的化合物，可作为潜在的抗肿瘤剂，并且包含这些化合物的药物组合物在pH为7.00的水相磷酸钠缓冲液中与小牛胸腺（CT）DNA的摩尔比为1:5时表现出结合亲和力。本发明还提供了一种制备C2-氟取代哌嗪连接的吡咯[2,1c][1-4]，苯二氮䓬的配方（IX）的方法。

  公开号：

  WO2009113084A1

文献信息

• Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted pyrrolo[2,1-c][1,4]benzodiazepines and their anticancer potential
  作者：Ahmed Kamal、Rajender、D. Rajasekhar Reddy、M. Kashi Reddy、G. Balakishan、T. Basha Shaik、Mukesh Chourasia、G. Narahari Sastry

  DOI：10.1016/j.bmc.2008.12.068

  日期：2009.2

  C2-Fluoro substituted DC-81, and its dimers that comprise of two C2-fluoro substituted DC-81 subunits tethered to their C8-position through simple alkane spacers as well as piperazine moiety side-armed with symmetrical alkyloxy spacers have been designed and synthesized. These fluoro substituted pyrrolo[2,1-c][1,4] benzodiazepines have shown remarkable DNA-binding ability and most of them possess promising anticancer activity, having GI(50) values in micromolar to nanomolar concentration range. DNA thermal denaturation studies show that some of these compounds (14a-c and 15) increase the Delta T-m values in the range of 28.9-38 degrees C, and this is further confirmed by the restriction endonuclease studies. This study illustrates the importance of introducing fluoro substitution at the C2-position apart from the incorporation of a piperazine ring in between the alkyloxy linker for enhancement of the DNA-binding ability in comparison to DSB-120 and SJG-136 (Delta T-m = 10.2 and 25.7 degrees C). Moreover, the variations in the DNA-binding ability with respect to fluoro substitution in this class of dimers has been investigated by molecular modeling studies. Some representative C2-fluoro substituted dimers (8a and 14a) have also exhibited significant anticancer activity in the 60 cancer cell line assay of the National Cancer Institute (NCI). (c) 2009 Elsevier Ltd. All rights reserved.
• [EN] C2-FLUORO SUBSTITUTED PIPERAZINE LINKED PYRROLO[2,1-C][1,4] BENZODIAZEPINE DIMERS AND A PROCESS FOR THE PREPARATION THEREOF<br/>[FR] DIMÈRES DE PYRROLO[2,1-C][1,4] BENZODIAZÉPINE LIÉS UN CYCLE PIPÉRAZINE SUBSTITUÉS PAR C2-FLUORÉ ET SON PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2009113084A1

  公开（公告）日：2009-09-17

  The present invention provides a compounds of general formula IXa-d, useful as potential antitumour agents and pharmaceutical composition comprising these compounds exhibits binding affinity with calf thymus (CT) DNA at a molar ratio of 1:5 in aqueous sodium phosphate buffer at pH of 7.00. The present invention further provides a process for the preparation of C2-Fluoro substituted piperazine linked pyrrolo[2,1c][1-4], benzodiazepine of formula (IX).

  本发明提供了一种一般式IXa-d的化合物，可作为潜在的抗肿瘤剂，并且包含这些化合物的药物组合物在pH为7.00的水相磷酸钠缓冲液中与小牛胸腺（CT）DNA的摩尔比为1:5时表现出结合亲和力。本发明还提供了一种制备C2-氟取代哌嗪连接的吡咯[2,1c][1-4]，苯二氮䓬的配方（IX）的方法。