(2S)-N-[4-(6-bromohexyloxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl dithioacetal | 1080662-00-5

• 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-(6-bromohexyloxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl dithioacetal
• 英文别名: 4-[(6-bromohexyl)oxy]-5-methoxy-2-nitrophenyl2-[di(ethylsulfanyl)methyl]tetrahydro-1H-1-pyrrolylmethanone；[(2S)-2-[bis(ethylsulfanyl)methyl]pyrrolidin-1-yl]-[4-(6-bromohexoxy)-5-methoxy-2-nitrophenyl]methanone
• CAS: 1080662-00-5
• 化学式: C₂₃H₃₅BrN₂O₅S₂
• 分子量: 563.577
• InChiKey: NTLFEULHKJKABL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-N-[4-(6-bromohexyloxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl dithioacetal 在 甲醇 、 tin(II) chloride dihdyrate 、 水 、 sodium hydride 、 calcium carbonate 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 (11aS)-7-methoxy-8-[6-(2-oxo-1,2-dihydrobenzo[c,d]indol-1-yl)hexoxy]-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one
  参考文献：
  名称：

  Design and synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine conjugates as potential anticancer agents

  摘要：

  A series of benzo[c,d]indol-2(1H)one-PBD conjugates (11a-I) have been designed and synthesized as potential anticancer agents. These compounds were prepared by linking the C8-position of DC-81 with a benzo[c,d]indol-2(1H)one moiety through different alkane spacers in good yields and confirmed by H-1 NMR, mass and HRMS data. The DNA binding ability of these conjugates was evaluated by thermal denaturation studies and interestingly, compound 111 showed enhanced DNA binding ability. These compounds were also evaluated for their anticancer activity in selected human cancer cell lines of lung, skin, colon and prostate by using MTT assay method. These new conjugates showed promising anticancer activity with IC50 values ranging from 1.05 to 36.49 mu M. Moreover, cell cycle arrest in SubG1 phase was observed upon treatment of A549 cells with 1 and 2 mu M (IC50) concentrations of compound 111 and it induced apoptosis. This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.003
• 作为产物：
  描述：

  1,6-二溴己烷 、 (2S)-N-(4-hydroxy-5-methoxy-2-nitrobenzoyl)pyrrolidine-2-carboxaldehyde diethyl thioacetal 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 生成 (2S)-N-[4-(6-bromohexyloxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl dithioacetal
  参考文献：
  名称：

  Design, synthesis and biological evaluation of imidazo[1,5-a]pyridine–PBD conjugates as potential DNA-directed alkylating agents

  摘要：

  一系列新型的咪唑[1,5-a]吡啶–PBD结合物被合成并评估了其在乳腺癌细胞系（MCF-7）中的抗肿瘤活性。有趣的是，所有化合物都表现出增强的DNA结合能力。这些结合物通过MTT细胞增殖实验显示出显著的抗肿瘤活性，其中化合物13f和13g表现出良好的抗肿瘤活性。处理乳腺癌细胞（MCF-7）时，使用2 μM浓度的这些化合物观察到了G2/M期细胞周期停滞。此外，当其浓度增加到4 μM时，观察到细胞在G0（凋亡）期的积累。这些化合物还诱导了参与凋亡和DNA损伤的蛋白质的表达，如p53、p21和γ-H2AX。对化合物13g与DNA的结合进行的计算机模拟结合研究帮助我们理解了相互作用的模式，我们观察到化合物13g与DNA小沟结合良好。

  DOI：

  10.1039/c2md20219k

文献信息

• Synthesis and biological evaluation of cinnamido linked pyrrolo[2,1-c][1,4]benzodiazepines as antimitotic agents
  作者：Ahmed Kamal、G. Balakishan、G. Ramakrishna、T. Basha Shaik、K. Sreekanth、M. Balakrishna、Rajender、D. Dastagiri、Shasi V. Kalivendi

  DOI：10.1016/j.ejmech.2010.05.041

  日期：2010.9

  A series of new cinnamido-pyrrolo[2,1-c][1,4)benzodiazepine conjugates (4a-d and 5a-d) and their dimers (6a-d) have been designed, synthesized and evaluated for their biological activity. The anticancer screening of compound 4a by the NCI exhibited significant GI50 values ranging from 68 to 732 nM against 53 of 59 human cancer cell lines tested. Compounds 5a-d and 6a-d have also shown remarkable cytotoxic activity with GI50 values <0.1 mu M concentrations in a large number of cell lines. Interestingly, compounds 5b and 6b have been identified as a new class of inhibitors of tubulin polymerization and their action has been rationalized by the cell cycle arrest in GO and G2/M phase. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis of C8–C8/C2–C8-linked triazolo pyrrolobenzodiazepine dimers by employing ‘click’ chemistry and their DNA-binding affinity
  作者：Ahmed Kamal、S. Prabhakar、N. Shankaraiah、Ch. Ratna Reddy、P. Venkat Reddy

  DOI：10.1016/j.tetlet.2008.04.006

  日期：2008.5

  A series of 1,2,3-triazole-containing pyrrolo[2,1-c][1,4]benzodiazepine dimers have been prepared efficiently by employing a 'click' chemistry protocol. This method involves 1,3-dipolar cycloaddition of terminal alkynes with organic azides using a Cu(I)-catalyst. Further, these molecules exhibited interesting DNA-binding affinity profiles. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis, anticancer activity and apoptosis inducing ability of anthranilamide-PBD conjugates
  作者：Ahmed Kamal、E. Vijaya Bharathi、M. Janaki Ramaiah、J. Surendranadha Reddy、D. Dastagiri、A. Viswanath、Farheen Sultana、S.N.C.V.L. Pushpavalli、Manika Pal-Bhadra、Aarti Juvekar、Subrata Sen、Surekha Zingde

  DOI：10.1016/j.bmcl.2010.04.037

  日期：2010.6

  A series of novel anthranilamide linked pyrrolo[2,1-c][1,4] benzodiazepine conjugates were prepared and evaluated for their anticancer activity. The effects of three promising PBD conjugates on cell cycle of cancerous cell line A375 were investigated. These promising compounds showed the characteristic features of apoptosis like enhancement in the levels of p53 and activation of caspase-3. (C) 2010 Elsevier Ltd. All rights reserved.
• Design and synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine conjugates as potential anticancer agents
  作者：Ahmed Kamal、G. Ramakrishna、V. Lakshma Nayak、P. Raju、A.V. Subba Rao、A. Viswanath、M.V.P.S. Vishnuvardhan、Sistla Ramakrishna、G. Srinivas

  DOI：10.1016/j.bmc.2011.12.003

  日期：2012.1

  A series of benzo[c,d]indol-2(1H)one-PBD conjugates (11a-I) have been designed and synthesized as potential anticancer agents. These compounds were prepared by linking the C8-position of DC-81 with a benzo[c,d]indol-2(1H)one moiety through different alkane spacers in good yields and confirmed by H-1 NMR, mass and HRMS data. The DNA binding ability of these conjugates was evaluated by thermal denaturation studies and interestingly, compound 111 showed enhanced DNA binding ability. These compounds were also evaluated for their anticancer activity in selected human cancer cell lines of lung, skin, colon and prostate by using MTT assay method. These new conjugates showed promising anticancer activity with IC50 values ranging from 1.05 to 36.49 mu M. Moreover, cell cycle arrest in SubG1 phase was observed upon treatment of A549 cells with 1 and 2 mu M (IC50) concentrations of compound 111 and it induced apoptosis. This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis. (C) 2011 Elsevier Ltd. All rights reserved.
• Design, synthesis and biological evaluation of imidazo[1,5-a]pyridine–PBD conjugates as potential DNA-directed alkylating agents
  作者：Ahmed Kamal、G. Ramakrishna、M. Janaki Ramaiah、A. Viswanath、A. V. Subba Rao、Chandrakant Bagul、Debasmitha Mukhopadyay、S. N. C. V. L. Pushpavalli、Manika Pal-Bhadra

  DOI：10.1039/c2md20219k

  日期：——

  A series of novel imidazo[1,5-a]pyridine–PBD conjugates were synthesized and evaluated for their antitumor activity in breast cancer cell line (MCF-7). Interestingly, all the compounds showed enhanced DNA binding ability. These conjugates showed significant antitumor activity as deduced by MTT cell proliferation assay and amongst them, compounds 13f and 13g exhibit promising antitumor activity. G2/M phase cell cycle arrest was observed on the treatment of breast cancer cells (MCF-7) with 2 μM concentration of these compounds. Moreover, accumulation of cells in the G0 (apoptotic) phase was observed upon increase of their concentration to 4 μM. These compounds also induced the expression of proteins involved in apoptosis and DNA damage such as p53, p21 and γ-H2AX. In silico binding studies of compound 13g with DNA was performed to understand the mode of interactions and we observed that compound 13g binds well with the minor groove of DNA.

  一系列新型的咪唑[1,5-a]吡啶–PBD结合物被合成并评估了其在乳腺癌细胞系（MCF-7）中的抗肿瘤活性。有趣的是，所有化合物都表现出增强的DNA结合能力。这些结合物通过MTT细胞增殖实验显示出显著的抗肿瘤活性，其中化合物13f和13g表现出良好的抗肿瘤活性。处理乳腺癌细胞（MCF-7）时，使用2 μM浓度的这些化合物观察到了G2/M期细胞周期停滞。此外，当其浓度增加到4 μM时，观察到细胞在G0（凋亡）期的积累。这些化合物还诱导了参与凋亡和DNA损伤的蛋白质的表达，如p53、p21和γ-H2AX。对化合物13g与DNA的结合进行的计算机模拟结合研究帮助我们理解了相互作用的模式，我们观察到化合物13g与DNA小沟结合良好。