N-acridin-9-yl-benzene-1,4-diamine | 58658-15-4

• 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: N-acridin-9-yl-benzene-1,4-diamine
• 英文别名: 9-(3-aminoanilino)acridine；ACRIDINE, 9-(m-AMINOANILINO)-；3-N-acridin-9-ylbenzene-1,3-diamine
• CAS: 58658-15-4
• 化学式: C₁₉H₁₅N₃
• 分子量: 285.348
• InChiKey: WXROLRGGANVSPA-UHFFFAOYSA-N

物化性质

• 熔点：
  266 °C (decomp)
• 沸点：
  493.5±30.0 °C(Predicted)
• 密度：
  1.301±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-acridin-9-yl-benzene-1,4-diamine 在 盐酸 、 sodium nitrite 、 sodium azide 作用下， 以82%的产率得到9-(3-azidoanilino)acridine
  参考文献：
  名称：

  Antitumor Polycyclic Acridines. 7. Synthesis and Biological Properties of DNA Affinic Tetra- and Pentacyclic Acridines

  摘要：

  New synthetic routes to a series of tetra- and pentacyclic acridines related in structure to marine natural products are reported. The novel water-soluble agent dihydroindolizino[7,6,5-kL]acridinium chloride 14 has inhibitory activity in a panel of non-small-cell lung and breast tumor cell lines exceeding that of m-AMSA. The salt inhibited the release of minicircle products of kDNA confirming that disorganization of topoisomerase II partly underlies the activity of the compound. COMPARE analysis of the NCI mean graph profile of compound 14 at the GI(50) level corroborates this conclusion with Pearson correlation coefficients (>0.6) to clinical agents of the topoisomerase II class: however, this correlation was not seen at the LC50 level. The inhibitory action of 14 on Saccharomyces cerevisiae transfected with human topoisomerase II isoforms showed a 3-fold selectivity against the II alpha isoform over the II beta isoform. Unlike nt-AMSA, 14 is not susceptible to P-glycoprotein-mediated drug efflux and retains activity in lung cells with derived resistance to the topoisomerase II inhibitor etoposide.

  DOI：

  10.1021/jm9909490
• 作为产物：
  描述：

  9-氯吖啶 、 间苯二胺 在 N-甲基吡咯烷酮 、 盐酸 作用下， 反应 24.0h， 以73%的产率得到N-acridin-9-yl-benzene-1,4-diamine
  参考文献：
  名称：

  Synthesis and SAR study of acridine, 2-methylquinoline and 2-phenylquinazoline analogues as anti-prion agents

  摘要：

  Transmissible spongiform encephalopathies (TSEs) are thought to arise from aggregation of a protease resistant protein denoted PrPSc, which is a misfolded isoform of the normal cellular prion protein PrPC. Using virtual high-throughput screening we have selected structures analogous to acridine, 2-methyquinoline and 2-phenylquinazoline as potential therapeutic candidates for the treatment of TSEs. From the synthesis and screening of constructed libraries we have shown that an electron-rich aromatic ring attached through an amine linker to the position para to the ring nitrogen is beneficial to both binding to PrPC and the suppression of PrPSc accumulation for acridine and 2-methylquinoline analogues. 2-Phenylquinazoline analogues appear to utilise a different mode of action by binding at a different location and/or pose. We report IC(50)s in the nanomolar range. (c) 2006 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.05.002

文献信息

• [EN] NOVEL HDMX INHIBITORS AND THEIR USE FOR CANCER TREATMENT<br/>[FR] NOUVEAUX INHIBITEURS HDMX ET LEUR UTILISATION DANS LE TRAITEMENT DU CANCER
  申请人：MIRX PHARMACEUTICALS LLC

  公开号：WO2015153535A1

  公开（公告）日：2015-10-08

  The present invention provides for novel acridine-like class of compounds that have demonstrated efficiency in treating cancer. The compounds of the present invention have demonstrated efficacy in binding to and antagonizing the activity of the p53 repressor, HDMX. Once administered to a cell, the compounds of the present invention bind HDMX, thereby allowing p53 to induce apoptosis of the cancerous cell. A combination of this class of compounds along with Nutlin3 provides a novel approach to treat cancers.

  本发明提供了一种新型的类似于吖啶的化合物，已经证明可以有效地治疗癌症。本发明的化合物已经证明在结合并拮抗p53抑制剂HDMX的活性方面具有疗效。一旦这些化合物被注入细胞，它们会与HDMX结合，从而使p53诱导癌细胞凋亡。将这类化合物与Nutlin3结合使用可以提供一种治疗癌症的新方法。
• HDMX inhibitors and their use for cancer treatment
  申请人：MIRX PHARMACEUTICALS, LLC

  公开号：US10183912B2

  公开（公告）日：2019-01-22

  The present invention provides for novel acridine-like class of compounds that have demonstrated efficiency in treating cancer. The compounds of the present invention have demonstrated efficacy in binding to and antagonizing the activity of the p53 repressor, HDMX. Once administered to a cell, the compounds of the present invention bind HDMX, thereby allowing p53 to induce apoptosis of the cancerous cell. A combination of this class of compounds along with Nutlin3 provides a novel approach to treat cancers.

  本发明提供了新型吖啶类化合物，这些化合物已证明可有效治疗癌症。本发明的化合物在与 p53 抑制剂 HDMX 结合并拮抗其活性方面具有显著疗效。一旦给细胞用药，本发明的化合物就会与 HDMX 结合，从而使 p53 能够诱导癌细胞凋亡。这类化合物与 Nutlin3 的结合提供了一种治疗癌症的新方法。
• NOVEL HDMX INHIBITORS AND THEIR USE FOR CANCER TREATMENT
  申请人：MIRX PHARMACEUTICALS, LLC

  公开号：US20170022166A1

  公开（公告）日：2017-01-26

  The present invention provides for novel acridine-like class of compounds that have demonstrated efficiency in treating cancer. The compounds of the present invention have demonstrated efficacy in binding to and antagonizing the activity of the p53 repressor, HDMX. Once administered to a cell, the compounds of the present invention bind HDMX, thereby allowing p53 to induce apoptosis of the cancerous cell. A combination of this class of compounds along with Nutlin3 provides a novel approach to treat cancers.
• Synthesis and SAR study of acridine, 2-methylquinoline and 2-phenylquinazoline analogues as anti-prion agents
  作者：H. Cope、R. Mutter、W. Heal、C. Pascoe、P. Brown、S. Pratt、B. Chen

  DOI：10.1016/j.ejmech.2006.05.002

  日期：2006.10

  Transmissible spongiform encephalopathies (TSEs) are thought to arise from aggregation of a protease resistant protein denoted PrPSc, which is a misfolded isoform of the normal cellular prion protein PrPC. Using virtual high-throughput screening we have selected structures analogous to acridine, 2-methyquinoline and 2-phenylquinazoline as potential therapeutic candidates for the treatment of TSEs. From the synthesis and screening of constructed libraries we have shown that an electron-rich aromatic ring attached through an amine linker to the position para to the ring nitrogen is beneficial to both binding to PrPC and the suppression of PrPSc accumulation for acridine and 2-methylquinoline analogues. 2-Phenylquinazoline analogues appear to utilise a different mode of action by binding at a different location and/or pose. We report IC(50)s in the nanomolar range. (c) 2006 Elsevier Masson SAS. All rights reserved.
• Antitumor Polycyclic Acridines. 7. Synthesis and Biological Properties of DNA Affinic Tetra- and Pentacyclic Acridines
  作者：Johnson Stanslas、Damien J. Hagan、Michael J. Ellis、Claire Turner、James Carmichael、Wynne Ward、Timothy R. Hammonds、Malcolm F. G. Stevens

  DOI：10.1021/jm9909490

  日期：2000.4.1

  New synthetic routes to a series of tetra- and pentacyclic acridines related in structure to marine natural products are reported. The novel water-soluble agent dihydroindolizino[7,6,5-kL]acridinium chloride 14 has inhibitory activity in a panel of non-small-cell lung and breast tumor cell lines exceeding that of m-AMSA. The salt inhibited the release of minicircle products of kDNA confirming that disorganization of topoisomerase II partly underlies the activity of the compound. COMPARE analysis of the NCI mean graph profile of compound 14 at the GI(50) level corroborates this conclusion with Pearson correlation coefficients (>0.6) to clinical agents of the topoisomerase II class: however, this correlation was not seen at the LC50 level. The inhibitory action of 14 on Saccharomyces cerevisiae transfected with human topoisomerase II isoforms showed a 3-fold selectivity against the II alpha isoform over the II beta isoform. Unlike nt-AMSA, 14 is not susceptible to P-glycoprotein-mediated drug efflux and retains activity in lung cells with derived resistance to the topoisomerase II inhibitor etoposide.