(2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal | 950191-35-2

• 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: (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal
• 英文别名: (2S)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]-4,4-difluoropyrrolidine-2-carboxaldehyde diethyl-dithioacetal；[(2S)-2-[bis(ethylsulfanyl)methyl]-4,4-difluoropyrrolidin-1-yl]-(4-hydroxy-5-methoxy-2-nitrophenyl)methanone
• CAS: 950191-35-2
• 化学式: C₁₇H₂₂F₂N₂O₅S₂
• 分子量: 436.501
• InChiKey: ZIRJHFOLPLMFJP-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  146
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal 在 copper(ll) sulfate pentahydrate 、 tin(II) chloride dihdyrate 、 potassium carbonate 、 sodium ascorbate 、 calcium carbonate 、 mercury dichloride 作用下， 以 甲醇 、 水 、 丙酮 、 乙腈 、 叔丁醇 为溶剂， 反应 26.0h， 生成 (6aS)-8,8-difluoro-3-[[1-[3-[[(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl]oxy]propyl]triazol-4-yl]methoxy]-2-methoxy-7,9-dihydro-6aH-pyrrolo[2,1-c][1,4]benzodiazepin-11-one
  参考文献：
  名称：

  雌二醇连接的吡咯并[2,1- c ] [1,4]苯并二氮杂（PBD）缀合物作为潜在抗癌药的合成及生物学评价

  摘要：

  一系列新的雌二醇连接的吡咯并[2,1- c ] [1,4]苯并二氮杂（E 2 -PBD）结合物（3a – f，4a–f和5a – f）具有不同的连接结构，包括三唑部分。设计和合成。已经对所有18种化合物的抗癌活性进行了评估，并且观察到某些化合物，特别是4c – e和5c，d表现出显着的抗癌活性。为了了解这些缀合物的作用机理，已经研究了与细胞周期效应和微管蛋白解聚活性有关的详细生物学方面。在所有这些缀合物中，化合物5c之一被认为是最有效的化合物，尤其是针对MCF-7乳腺癌细胞系。

  DOI：

  10.1016/j.bmc.2011.03.015
• 作为产物：
  描述：

  (2S)-N-(4-benzyloxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal 在 三氟化硼乙醚 、 乙硫醇 作用下， 以 二氯甲烷 为溶剂， 以78%的产率得到(2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal
  参考文献：
  名称：

  Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted pyrrolo[2,1-c][1,4]benzodiazepines and their anticancer potential

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.12.068

文献信息

• [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。
• Novel bis-2-difluoro-pyrrolo[2,1-C][1,4]benzodiazepine dimmers
  申请人：Kamal Ahmed

  公开号：US20070249828A1

  公开（公告）日：2007-10-25

  The present invention provides a novel bis 2-difluoro pyrrolo[2,1-c][1,4]benzodiazepine of formula VII wherein, n is 3 to 10. novel bis 2-difluoro pyrrolo[2,1-c][1,4]benzodiazepine of formula VII exhibits biding affinity with calf thymus (CT) DNA at a molar ratio of 1:5 in aqueous sodium phosphate buffer at pH of about 7.00. The present invention further provides a process for the preparation of novel bis 2-difluoro pyrrolo[2,1-c][1,4]benzodiazepine of formula VII.

  本发明提供了一种新型的式子为VII的双2-二氟吡咯并[2,1-c][1,4]苯二氮平，其中n为3至10。新型的式子为VII的双2-二氟吡咯并[2,1-c][1,4]苯二氮平在pH约为7.00的水溶性磷酸钠缓冲液中，与小牛胸腺（CT）DNA以1:5的摩尔比结合亲和力。本发明还提供了一种制备新型的式子为VII的双2-二氟吡咯并[2,1-c][1,4]苯二氮平的方法。
• WO2007/105045
  申请人：——

  公开号：——

  公开（公告）日：——
• NOVEL BIS-2-DIFLUORO-PYRROLO[2,1-C][1,4]BENZODIAZEPINE DIMMERS
  申请人：Council of Scientific and Industrial Research

  公开号：EP2001894B1

  公开（公告）日：2010-12-22
• C2-FLUORO SUBSTITUTED PIPERAZINE LINKED PYRROLO[2,1-C][1,4] BENZODIAZEPINE DIMERS AND A PROCESS FOR THE PREPARATION THEREOF
  申请人：Council Of Scientific & Industrial Research

  公开号：EP2271647B1

  公开（公告）日：2012-12-05