N¹-(acridin-9-yl)-6-methoxybenzene-1,3-diamine | 869058-72-0

• 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: N¹-(acridin-9-yl)-6-methoxybenzene-1,3-diamine
• 英文别名: 3-N-acridin-9-yl-4-methoxybenzene-1,3-diamine
• CAS: 869058-72-0
• 化学式: C₂₀H₁₇N₃O
• 分子量: 315.374
• InChiKey: BDDYRHGAJGJJMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  60.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N¹-(acridin-9-yl)-6-methoxybenzene-1,3-diamine 、 p-isocyanophenyl mustard 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以80.4%的产率得到1-[3-(Acridin-9-ylamino)-4-methoxyphenyl]-3-[4-[bis(2-chloroethyl)amino]phenyl]urea
  参考文献：
  名称：

  稳定和有效的抗肿瘤药苯胺氮芥的合成及其生物学活性，其通过尿素键与9-苯胺基cr啶连接。

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2008.04.024
• 作为产物：
  描述：

  2-氨基-4-硝基苯甲醚 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 、 乙醇 、 氯仿 为溶剂， -5.0~20.0 ℃ 、344.74 kPa 条件下， 反应 0.42h， 生成 N¹-(acridin-9-yl)-6-methoxybenzene-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

• Aniline or phenol mustards linked to DNA-affinic molecules or water-soluble aromatic rings and their use as cancer therapeutic agents
  申请人：Su Tsann-Long

  公开号：US20080171765A1

  公开（公告）日：2008-07-17

  New aniline or phenol N-mustards linked to DNA-affinity carriers (such as 9-anilinoacridines, acridines and quinolines), aminobenzamides or aminophenol ethers by a urea, carbamic acid, carbanic acid ester, hydrazineurea, hydrazinecarbamic acid ester, phenoxyurea, phenoxycarbamic acid ester linkage with improved chemical stability and anti-tumor therapeutic efficacy are provided.

  提供了与DNA亲和载体（如9-苯胺基吖啶、吖啶和喹啉）、氨基苯甲酰胺或氨基酚醚通过脲、碳酸酯、碳酸酯、叠氮脲、叠氮碳酸酯、苯氧基脲、苯氧基碳酸酯链接的新苯胺或酚N-芥子素，具有改善的化学稳定性和抗肿瘤治疗效果。
• PHENYL N-MUSTARD LINKED TO DNA-AFFINIC MOLECULES OR WATER-SOLUBLE ARYL RINGS, METHOD AND THEIR USE AS CANCER THERAPEUTIC AGENTS
  申请人：SU Tsann-Long

  公开号：US20130178494A1

  公开（公告）日：2013-07-11

  The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.

  本公开涉及新的DNA定向烷基化剂和具有改善化学稳定性和抗肿瘤治疗效果的水溶性N-芥子剂。
• 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.
• US8222297B2
  申请人：——

  公开号：US8222297B2

  公开（公告）日：2012-07-17
• US9193687B2
  申请人：——

  公开号：US9193687B2

  公开（公告）日：2015-11-24