1-{[4-(7-chloroquinolin-4-yl)piperazin-1-yl]methyl}indoline-2,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-{[4-(7-chloroquinolin-4-yl)piperazin-1-yl]methyl}indoline-2,3-dione
• 英文别名: 1-[4-(7-chloro-quinolin-4-yl)-piperazin-1-ylmethyl]-1hindole-2,3-dione；1-[[4-(7-Chloro-4-quinolyl)piperazin-1-yl]methyl]indoline-2,3-dione；1-[[4-(7-chloroquinolin-4-yl)piperazin-1-yl]methyl]indole-2,3-dione
• 化学式: C₂₂H₁₉ClN₄O₂
• 分子量: 406.871
• InChiKey: AMBVPNOXNNWHJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-{[4-(7-chloroquinolin-4-yl)piperazin-1-yl]methyl}indoline-2,3-dione 、 氨基硫脲 以 乙醇 为溶剂， 反应 3.0h， 生成 N¹-[4-(7-chloroquinolin-4-yl)piperazin-1-ylmethyl]-1H-indole-2,3-dione 3-thiosemicarbazone
  参考文献：
  名称：

  Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: A hybrid pharmacophore approach

  摘要：

  A novel class of 4-piperazinylquinoline derivatives based on the isatin scaffold were designed by molecular hybridization approach and synthesized for biological evaluation. Subsequently, the compounds were examined for their cytotoxic effects on two human breast tumor cell lines, MDA-MB468 and MCF7, and two non-cancer breast epithelial cell lines, 184B5 and MCF10A. Although all compounds examined were quite effective on the breast cancer cell lines examined, the compound 4-bromo-1-[4(7-chloro-quinolin-4-yl)-piperazin-1-ylmethyl]-1H-indole-2,3-dione (5b) and N-1-[4-(7-trifluoromethylquinolin4-yl)]-piperazin-1-ylmethyl-4-chloro-1H-indole-2,3-dione-3-thiosemicarbazone (8a) emerged as the most active among this series. It appeared that both 5b and 8a caused apoptosis to MCF7 cancer cells, but not MCF10A non-cancer cells. Thus, 4-piperazinylquinoline linked isatin analog can serve as the prototype molecule for further development of a new class of anti-breast cancer agents. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.001
• 作为产物：
  描述：

  4,7-二氯喹啉 在 potassium carbonate 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 水 为溶剂， 反应 7.0h， 生成 1-{[4-(7-chloroquinolin-4-yl)piperazin-1-yl]methyl}indoline-2,3-dione
  参考文献：
  名称：

  Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives

  摘要：

  A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum. These derivatives showed anti-plasmodial IC50 values in the ranges of 1.3-0.079 and 2.0-0.050 mu M against a chloroquine-sensitive (D10) and two resistant (K1 and W2) strains of P. falciparum, respectively. In order to determine potential targets for this class of compounds in P. falciparum, selected compounds were also tested against the parasitic cysteine protease falcipain-2. In terms of further development of this class of isatin derivatives, two of the compounds based on a flexible alkyl chain linker and a thiosemicarbazone moiety warrant further investigation as potential anti-plasmodial leads. These two derivatives showed good in vitro activity against K1 and W2 with IC50 values of 51 and 54 nM, respectively, while retaining potency against the D10 strain with IC50 values of 79 and 95 nM, respectively. Generally speaking, the inhibitory potency of all compounds in the series against the parasites did not strongly correlate with inhibitory potency against falcipain-2 for selected compounds tested, which at best was weak to moderate, suggesting other mechanisms of inhibition may also be involved or compounds may be selectively taken up by Plasmodium falciparum. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.037

文献信息

• New N-Mannich bases obtained from isatin and piperazine derivatives: the synthesis and evaluation of antimicrobial activity
  作者：Andrei V. Bogdanov、Al’bina M. Vazykhova、Nadezhda R. Khasiyatullina、Dmitry B. Krivolapov、Alexey B. Dobrynin、Alexandra D. Voloshina、Vladimir F. Mironov

  DOI：10.1007/s10593-016-1826-6

  日期：2016.1

  A Mannich reaction of isatin with monosubstituted piperazines in the presence of aqueous formaldehyde was used to synthesize new, as well as two previously described derivatives of 1-piperazinomethylisatins, which were further converted to isoindigo derivatives. The antimicrobial activity of the obtained heterocycles was evaluated.

  在含水甲醛的存在下，靛红与单取代的哌嗪的曼尼希反应用于合成新的以及先前描述的1-哌嗪子甲基靛红的两种衍生物，然后将其进一步转化为异靛蓝衍生物。评价得到的杂环的抗菌活性。
• Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: A hybrid pharmacophore approach
  作者：V. Raja Solomon、Changkun Hu、Hoyun Lee

  DOI：10.1016/j.bmc.2010.01.001

  日期：2010.2

  A novel class of 4-piperazinylquinoline derivatives based on the isatin scaffold were designed by molecular hybridization approach and synthesized for biological evaluation. Subsequently, the compounds were examined for their cytotoxic effects on two human breast tumor cell lines, MDA-MB468 and MCF7, and two non-cancer breast epithelial cell lines, 184B5 and MCF10A. Although all compounds examined were quite effective on the breast cancer cell lines examined, the compound 4-bromo-1-[4(7-chloro-quinolin-4-yl)-piperazin-1-ylmethyl]-1H-indole-2,3-dione (5b) and N-1-[4-(7-trifluoromethylquinolin4-yl)]-piperazin-1-ylmethyl-4-chloro-1H-indole-2,3-dione-3-thiosemicarbazone (8a) emerged as the most active among this series. It appeared that both 5b and 8a caused apoptosis to MCF7 cancer cells, but not MCF10A non-cancer cells. Thus, 4-piperazinylquinoline linked isatin analog can serve as the prototype molecule for further development of a new class of anti-breast cancer agents. (C) 2010 Elsevier Ltd. All rights reserved.
• Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives
  作者：Idan Chiyanzu、Cailean Clarkson、Peter J. Smith、Julie Lehman、Jiri Gut、Philip J. Rosenthal、Kelly Chibale

  DOI：10.1016/j.bmc.2005.02.037

  日期：2005.5

  A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum. These derivatives showed anti-plasmodial IC50 values in the ranges of 1.3-0.079 and 2.0-0.050 mu M against a chloroquine-sensitive (D10) and two resistant (K1 and W2) strains of P. falciparum, respectively. In order to determine potential targets for this class of compounds in P. falciparum, selected compounds were also tested against the parasitic cysteine protease falcipain-2. In terms of further development of this class of isatin derivatives, two of the compounds based on a flexible alkyl chain linker and a thiosemicarbazone moiety warrant further investigation as potential anti-plasmodial leads. These two derivatives showed good in vitro activity against K1 and W2 with IC50 values of 51 and 54 nM, respectively, while retaining potency against the D10 strain with IC50 values of 79 and 95 nM, respectively. Generally speaking, the inhibitory potency of all compounds in the series against the parasites did not strongly correlate with inhibitory potency against falcipain-2 for selected compounds tested, which at best was weak to moderate, suggesting other mechanisms of inhibition may also be involved or compounds may be selectively taken up by Plasmodium falciparum. (c) 2005 Elsevier Ltd. All rights reserved.