(2S,4R)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]-4-fluoropyrrolidine-2-carboxaldehyde diethyl-dithioacetal | 929049-05-8

• 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,4R)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]-4-fluoropyrrolidine-2-carboxaldehyde diethyl-dithioacetal
• 英文别名: (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)-4-fluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal
• CAS: 929049-05-8
• 化学式: C₁₇H₂₃FN₂O₅S₂
• 分子量: 418.51
• InChiKey: QGCXNRHBANUIBO-MFKMUULPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  92.91
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (2S,4R)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]-4-fluoropyrrolidine-2-carboxaldehyde diethyl-dithioacetal 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,8R)-8-fluoro-3-[[1-[5-[[(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]pentyl]triazol-4-yl]methoxy]-2-methoxy-6a,7,8,9-tetrahydropyrrolo[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,4R)-N-(4-benzyloxy-5-methoxy-2-nitrobenzoyl)-4-fluoropyrrolidine-2-carboxaldehyde diethyl thioacetal 在 EtSH*BF₃OEt₂ 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以80%的产率得到(2S,4R)-N-[4-hydroxy-5-methoxy-2-nitrobenzoyl]-4-fluoropyrrolidine-2-carboxaldehyde diethyl-dithioacetal
  参考文献：
  名称：

  Synthesis and DNA-binding ability of C2R-fluoro substituted DC-81 and its dimers

  摘要：

  C2R-Fluoro substituted DC-81 and its dimers have been synthesized that exhibit significant DNA-binding ability, particularly the five carbon alkane spacer compound (6c) showed the helix melting temperature (Delta T-m) of 18.8 degrees C after incubation of 36 h at 37 degrees C. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.070

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.