4-methoxy-N1-(4-methylacridin-9-yl)benzene-1,3-diamine | 869058-68-4

• 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-N1-(4-methylacridin-9-yl)benzene-1,3-diamine
• 英文别名: 4-methoxy-N¹-(4-methylacridin-9-yl)benzene-1,3-diamine
• CAS: 869058-68-4
• 化学式: C₂₁H₁₉N₃O
• 分子量: 329.401
• InChiKey: NBZVUDKLBMACLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.03
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  60.17
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-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47%的产率得到[2-methoxy-5-(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
• 作为产物：
  描述：

  4-methyl-9-chloroacridine 、 2,4-diaminoanisole dihydrochloride 在 N-甲基吗啉 作用下， 以 乙醇 、 氯仿 为溶剂， 生成 4-methoxy-N1-(4-methylacridin-9-yl)benzene-1,3-diamine
  参考文献：
  名称：

  Synthesis and antitumor activity of 5-(9-acridinylamino)anisidine derivatives

  摘要：

  A series of 5-(9-acridinylamino)anisidines were synthesized by condensing methoxy-substituted 1,3-phenylenediamines (10 and 11) with 9-chloroacridine derivatives to form 5-(9-acridinylamino)-m-anisidines (AMAs, 14a-e) and 5-(9-acridinylamino)-o-anisidines (AOAs, 15a-e). 5-(9-Acridinylamino)-p-anisidines (APAs, 17a-e) were synthesized by reacting 2-methoxy-5-nitroaniline (12) with 9-anilinoacridines, followed by reduction. The cytotoxic inhibition of growth of various human tumor cells in culture, inhibitory effects against topoisomerase II, and DNA interaction of these agents were studied. The structure-activity relationship studies revealed the following degree of potency: AOAs > AMAs > APAs. They also revealed that the newly synthesized derivatives bearing CONH2NH2NMe2 and Me substituents at C4 and C5 positions of the acridine chromophore (i.e., AMA 14e, AOA 15e, and APA 17e) exhibited significant cytotoxicity against human tumor cell growth in vitro. AOA (15e) was the most potent among these derivatives, which resulted in 60% suppression of tumor volume at a dose of 20 mg/kg (Q2D x 9), intravenous injection on day 26 in nude mice bearing human breast carcinoma MX-1 xenografts. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.018

文献信息

• Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage
  作者：Naval Kapuriya、Kalpana Kapuriya、Xiuguo Zhang、Ting-Chao Chou、Rajesh Kakadiya、Yu-Tse Wu、Tung-Hu Tsai、Yu-Ting Chen、Te-Chang Lee、Anamik Shah、Yogesh Naliapara、Tsann-Long Su

  DOI：10.1016/j.bmc.2008.04.024

  日期：2008.5

  synthesized and evaluated for antitumor studies. The new N-mustard derivatives were prepared by the reaction of 4-bis(2-chloroethyl)aminophenyl isocyanate with a variety of 9-anilinoacridines or 9-aminoacridine. The antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro without cross-resistance to taxol or vinblastine and showed potent antitumor therapeutic efficacy in nude

  为了提高N-芥末的化学稳定性和治疗效果，合成了一系列通过尿素接头与DNA亲和性9-苯胺基cr啶和​​and啶连接的苯基N-芥末，并进行了抗肿瘤研究。通过使4-双（2-氯乙基）氨基苯基异氰酸酯与各种9-苯胺基cr啶或9-氨基ac啶反应制备新的N-芥末衍生物。抗肿瘤研究表明，这些药物在体外显示出有效的细胞毒性，而对紫杉醇或长春碱没有交叉耐药性，并且在裸鼠中对人肿瘤异种移植物显示出有效的抗肿瘤治疗功效。还表明24d通过彗星试验能够诱导明显的剂量依赖性DNA交联水平，并且在大鼠血浆中具有长的半衰期。