(2S)-N-(4-benzyloxy-5-methoxy-2-aminobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal | 1145663-12-2

• 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-benzyloxy-5-methoxy-2-aminobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal
• CAS: 1145663-12-2
• 化学式: C₂₄H₃₀F₂N₂O₃S₂
• 分子量: 496.643
• InChiKey: UZPAUDLZDAXWKZ-IBGZPJMESA-N

物化性质

• 沸点：
  662.0±55.0 °C(predicted)
• 密度：
  1.29±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.54
• 重原子数：
  33.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.79
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S)-N-(4-benzyloxy-5-methoxy-2-aminobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal 在 calcium carbonate 、 mercury dichloride 作用下， 以 水 、 乙腈 为溶剂， 以60%的产率得到(11as)-2,2-difluoro-8-benzyloxy-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one
  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
• 作为产物：
  描述：

  (2S)-N-(4-benzyloxy-5-methoxy-2-nitrobenzoyl)-4,4-difluoropyrrolidine-2-carboxaldehyde di(ethylthio)acetal 在 甲醇 、 tin(II) chloride dihdyrate 作用下， 以88%的产率得到(2S)-N-(4-benzyloxy-5-methoxy-2-aminobenzoyl)-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