[4-methoxy-3-(4-methylacridin-9-ylamino)phenyl]carbamic acid 4-[bis(2-chloroethyl)amino]phenyl ester | 1138347-69-9

• 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: [4-methoxy-3-(4-methylacridin-9-ylamino)phenyl]carbamic acid 4-[bis(2-chloroethyl)amino]phenyl ester
• 英文别名: [4-[bis(2-chloroethyl)amino]phenyl] N-[4-methoxy-3-[(4-methylacridin-9-yl)amino]phenyl]carbamate
• CAS: 1138347-69-9
• 化学式: C₃₂H₃₀Cl₂N₄O₃
• 分子量: 589.521
• InChiKey: MUXDTSNURGUAQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  75.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-methoxy-N1-(4-methylacridin-9-yl)benzene-1,3-diamine 、 carbonic acid p-(bis-2-chloroethylamino)phenol ester-p-nitrophenyl ester 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以52%的产率得到[4-methoxy-3-(4-methylacridin-9-ylamino)phenyl]carbamic acid 4-[bis(2-chloroethyl)amino]phenyl ester
  参考文献：
  名称：

  Novel DNA-directed alkylating agents: Design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker

  摘要：

  A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies revealed that these derivatives possessed significant cytotoxicity with IC50 in sub-micromolar range in inhibiting human lymphoblastic leukemia (CCRF-CEM), breast carcinoma (MX-1), colon carcinoma (HCT-116) and human non-small cell lung cancer (H1299) cell growth in vitro. Compounds 10a, 10b, 10e, 10i, and 15a were selected for evaluating their antitumor activity in nude mice bearing MX1 and HCT-116 xenografts. Remarkably, total tumor remission was achieved by these agents with only one cycle of treatment. Interestingly, no tumor relapse was found in mice treated with 10a over 129 days. This agent is capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells in a dose dependent manner by modified comet assay and has a long half-life in rat plasma. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.022

文献信息

• Novel DNA-directed alkylating agents: Design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker
  作者：Naval Kapuriya、Kalpana Kapuriya、Huajin Dong、Xiuguo Zhang、Ting-Chao Chou、Yu-Ting Chen、Te-Chang Lee、Wen-Chuan Lee、Tung-Hu Tsai、Yogesh Naliapara、Tsann-Long Su

  DOI：10.1016/j.bmc.2008.12.022

  日期：2009.2

  A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies revealed that these derivatives possessed significant cytotoxicity with IC50 in sub-micromolar range in inhibiting human lymphoblastic leukemia (CCRF-CEM), breast carcinoma (MX-1), colon carcinoma (HCT-116) and human non-small cell lung cancer (H1299) cell growth in vitro. Compounds 10a, 10b, 10e, 10i, and 15a were selected for evaluating their antitumor activity in nude mice bearing MX1 and HCT-116 xenografts. Remarkably, total tumor remission was achieved by these agents with only one cycle of treatment. Interestingly, no tumor relapse was found in mice treated with 10a over 129 days. This agent is capable of inducing DNA interstrand cross-linking in human non-small lung cancer H1299 cells in a dose dependent manner by modified comet assay and has a long half-life in rat plasma. (c) 2008 Elsevier Ltd. All rights reserved.