methyl 5-methyl-11-(3-(3-phenylthioureido)propylamino)-5H-indolo[2,3-b]quinoline-9-carboxylate | 1445963-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 5-methyl-11-(3-(3-phenylthioureido)propylamino)-5H-indolo[2,3-b]quinoline-9-carboxylate
• 英文别名: methyl 5-methyl-11-[3-(phenylcarbamothioylamino)propylamino]indolo[2,3-b]quinoline-9-carboxylate
• CAS: 1445963-10-9
• 化学式: C₂₈H₂₇N₅O₂S
• 分子量: 497.621
• InChiKey: BLNPZIAMJLCNLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  80.21
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  methyl 11-chloro-5-methyl-5H-indolo[2,3-b]quinoline-9-carboxylate 以 四氢呋喃 为溶剂， 生成 methyl 5-methyl-11-(3-(3-phenylthioureido)propylamino)-5H-indolo[2,3-b]quinoline-9-carboxylate
  参考文献：
  名称：

  Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2,11-disubstituted indolo[2,3-b]quinolines

  摘要：

  This report describes the synthesis, and in vitro and in vivo antimalarial evaluations of certain ester-modified neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives. The modifications were carried out by introducing ester groups at the C2 and/or C9 position on the neocryptolepine core and the terminal amino group of the 3-aminopropylamine substituents at the C11 position with a urea/thiourea unit. The antiplasmodial activities of our derivative agents against two different strains (CQS: NF54, and CQR: R1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that the ester modified neocryptolepine derivatives have higher antiplasmodial activities against both strains and a low cytotoxic activity against normal cells. The best results were achieved by compounds 9c and 12b against the NF54 strain with the IC50/SI value as 2.27 nM/361 and 1.81 nM/321, respectively. While against R1 strain, all the tested compounds showed higher activity than the well-known antimalarial drug chloroquine. Furthermore, the compounds were tested for beta-haematin inhibition and 12 were found to be more active than chloroquine (IC50 = 18 mu M). Structure activity relationship studies exposed an interesting linear correlation between polar surface area of the molecule and beta-haematin inhibition for this series. In vivo testing of compounds 7 and 8a against NF54 strain on Plasmodium berghei female mice showed that the introduction of the ester group increased the antiplasmodial activity of the neocryptolepine core substantially. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.072

文献信息

• Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2,11-disubstituted indolo[2,3-b]quinolines
  作者：Wen-Jie Lu、Kathryn J. Wicht、Li Wang、Kento Imai、Zhen-Wu Mei、Marcel Kaiser、Ibrahim El Tantawy El Sayed、Timothy J. Egan、Tsutomu Inokuchi

  DOI：10.1016/j.ejmech.2013.03.072

  日期：2013.6

  This report describes the synthesis, and in vitro and in vivo antimalarial evaluations of certain ester-modified neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives. The modifications were carried out by introducing ester groups at the C2 and/or C9 position on the neocryptolepine core and the terminal amino group of the 3-aminopropylamine substituents at the C11 position with a urea/thiourea unit. The antiplasmodial activities of our derivative agents against two different strains (CQS: NF54, and CQR: R1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that the ester modified neocryptolepine derivatives have higher antiplasmodial activities against both strains and a low cytotoxic activity against normal cells. The best results were achieved by compounds 9c and 12b against the NF54 strain with the IC50/SI value as 2.27 nM/361 and 1.81 nM/321, respectively. While against R1 strain, all the tested compounds showed higher activity than the well-known antimalarial drug chloroquine. Furthermore, the compounds were tested for beta-haematin inhibition and 12 were found to be more active than chloroquine (IC50 = 18 mu M). Structure activity relationship studies exposed an interesting linear correlation between polar surface area of the molecule and beta-haematin inhibition for this series. In vivo testing of compounds 7 and 8a against NF54 strain on Plasmodium berghei female mice showed that the introduction of the ester group increased the antiplasmodial activity of the neocryptolepine core substantially. (C) 2013 Elsevier Masson SAS. All rights reserved.