9-chloro-4-fluoroacridine | 3829-32-1

• 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: 9-chloro-4-fluoroacridine
• CAS: 3829-32-1
• 化学式: C₁₃H₇ClFN
• 分子量: 231.657
• InChiKey: BKJLZFTZPLSXKS-UHFFFAOYSA-N

物化性质

• 熔点：
  142 °C
• 沸点：
  382.7±12.0 °C(Predicted)
• 密度：
  1.386±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-chloro-4-fluoroacridine 在 ammonium carbonate 、 乙酸酐 作用下， 生成 N-(4-fluoro-acridin-9-yl)-acetamide
  参考文献：
  名称：

  145.对氟取代的5-氨基ac啶及相关化合物的性质的研究。第一部分：一氟-5-氨基ac啶

  摘要：

  DOI：

  10.1039/jr9470000759
• 作为产物：
  描述：

  2-氟苯胺 在 硫酸 、 铜 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 9-chloro-4-fluoroacridine
  参考文献：
  名称：

  设计和合成一些cr啶-哌嗪杂种以改善认知功能障碍

  摘要：

  使用逐步降低的被动回避和乙酰胆碱酯酶生化评估支持的高架迷宫模型，设计，合成和评估了一系列cr啶-哌嗪杂种的认知潜能。氧化应激标志物的生化估计即。已经进行了血浆亚硝酸盐，硫代巴比妥酸反应性物质，过氧化氢酶，超氧化物歧化酶和谷胱甘肽的研究。对目标化合物5a-5m进行了进一步的计算机分析，以探索酶内的结合模式。

  DOI：

  10.1111/cbdd.13017

文献信息

• Potential antitumor agents. 47. 3'-Methylamino analogs of amsacrine with in vivo solid tumor activity
  作者：Graham J. Atwell、Bruce C. Baguley、Graeme J. Finlay、Gordon W. Rewcastle、William A. Denny

  DOI：10.1021/jm00159a035

  日期：1986.9

  antileukemic agent amsacrine with a 3'-methylamino group provides a compound (3) with a broader spectrum of action, including in vivo activity against experimental solid tumors. The synthesis, physicochemical properties, and biological activity of a series of acridine-substituted analogues of 3 are described. The compounds show higher levels of DNA binding, water solubility, and in vivo solid tumor activity

  用3'-甲基氨基取代临床抗白血病药物氨苯磺酸的3'-甲氧基提供了具有更广谱作用的化合物（3），包括针对实验性实体瘤的体内活性。描述了一系列3的a啶取代的类似物的合成，理化性质和生物学活性。这些化合物显示出更高的DNA结合水平，水溶性和体内实体瘤活性（刘易斯肺癌），而其氨色林对应物更高。然而，a啶取代的结构-活性关系是不同的，其中3,5-二取代的3'-甲基氨基化合物显示出最高的活性（与4,5-二取代的氨ac碱类似物相比）。
• Potential antitumor agents. 52. Carbamate analogs of amsacrine with in vivo activity against multidrug-resistant P388 leukemia
  作者：Gordon W. Rewcastle、Bruce C. Baguley、Graham J. Atwell、William A. Denny

  DOI：10.1021/jm00392a009

  日期：1987.9

  provided increased activity against the multidrug-resistant P388/ADR leukemia subline in vivo. Since activity against such resistant tumors is of great clinical significance, a series of acridine-substituted carbamate derivatives were evaluated against both wild-type and ADR/resistant P388 leukemia and the Lewis lung solid tumor in vivo. Structure-activity relationships for all three tumor lines were similar

  对一系列与抗白血病药物氨苯磺酸有关的苯胺取代的9-苯胺基cr啶的研究表明，1'-氨基甲酸酯基团在体内对多药耐药的P388 / ADR白血病亚系提供增强的活性。由于针对这种抗药性肿瘤的活性具有重要的临床意义，因此在体内针对野生型和ADR /抗药性P388白血病以及Lewis肺实体瘤评估了一系列of啶取代的氨基甲酸酯衍生物。所有三个肿瘤细胞系的结构活性关系相似，其中3-卤代-5-甲基和3-卤代5-甲氧基化合物被证明是活性最高的。这种取代模式还提供了最高的DNA结合。此类化合物（尤其是3-氯-5-甲基和3-氯-5-甲氧基）对野生型P388和Lewis肺具有体内活性，其活性与先前开发的最佳氨水analogue类似物相当（治愈率超过50％） ，以及P388 / ADR活动。这项工作从根本上完成了amsacrine系列抗肿瘤药的开发。
• Shining Visible Light on Reductive Elimination: Acridine–Pd-Catalyzed Cross-Coupling of Aryl Halides with Carboxylic Acids
  作者：Naoyuki Toriumi、Tomonori Inoue、Nobuharu Iwasawa

  DOI：10.1021/jacs.2c09318

  日期：2022.10.26

  Experimental mechanistic studies have proved that the reductive elimination of aryl esters is induced by photoirradiation of phosphinoacridine-ligated arylpalladium(II) carboxylate complexes. The theoretical calculation suggests that the reductive elimination in the excited state is promoted by decreasing the electron density of the Pd center through photoinduced intramolecular electron transfer, i.e., MLCT

  尽管最近在有机合成中过渡金属/光氧化还原双重催化取得了巨大进展，但在可见光照射下可以更有效地利用光能的单一过渡金属催化仍然不发达。在此，我们报告了用于可见光诱导的过渡金属催化的光敏膦吖啶双齿配体的设计，期望电子接受吖啶部分将产生高反应性缺电子金属中心，通过金属对配体电荷进行还原消除转移（MLCT）。使用这些配体，我们实现了钯催化的芳基卤化物与羧酸在可见光照射下的交叉偶联反应。膦基吖啶配体的电子调谐不仅能够在蓝光照射下使用各种芳基卤化物作为偶联配偶体，包括反应性较低的芳基氯，而且还实现了低能量绿光和红光的交叉使用耦合。实验机理研究证明，芳基酯的还原消除是由膦基吖啶-连接的芳基钯 (II) 羧酸盐配合物的光照射诱导的。理论计算表明，由于缺电子吖啶支架，在过渡态下，通过光诱导分子内电子转移（即 MLCT）降低 Pd 中心的电子密度，促进了激发态的还原消除。
• Potential antitumor agents. 48. 3'-Dimethylamino derivatives of amsacrine: redox chemistry and in vivo solid tumor activity
  作者：Graham J. Atwell、Gordon W. Rewcastle、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00387a012

  日期：1987.4

  Structure-activity relationships for a series of acridine-substituted 3'-N(CH3)2 derivatives of the clinical antileukemic drug amsacrine (1) are reported. The parent (unsubstituted) compound 3 has activity against the Lewis lung solid tumor that is superior to amsacrine (1), the new clinical amsacrine analogue 4, and the recently developed 3'-NHCH3 derivative 2. Although the compounds generally bind less well to DNA and are less dose potent in vivo than either their amsacrine (3'-OCH3) or 3'-NHCH3 analogues, they show very high levels of antitumor activity, with the 4-OCH3 derivative capable of effecting 100% cures of the Lewis lung solid tumor. The broad structure-activity relationships for acridine substitution more closely resemble those of the amsacrine than the 3'-NHCH3 series, with 4-substituted and 4,5-disubstituted compounds showing the highest activity.
• Synthesis and Structure−Activity Relationships of Potential Anticancer Agents:  Alkylcarbamates of 3-(9-Acridinylamino)-5-hydroxymethylaniline
  作者：Tsann-Long Su、Ching-Huang Chen、Lin-Fei Huang、Chao-Hao Chen、Manas K. Basu、Xiu-Guo Zhang、Ting-Chao Chou

  DOI：10.1021/jm9901226

  日期：1999.11.1

  A series of potential 9-anilinoacridine antitumor agents, 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) derivatives with monosubstituent at C4' and disubstituents at C4' and C5' of the acridine ring and their alkylcarbamates, were synthesized for evaluation of their antitumor activity. A structure-activity relationship (SAR) study showed that the AHMA-alkylcarbamates were more potent than their corresponding parent AHMA compounds. In addition, the cytotoxicity of the AHMA-alkylcarbamate decreased with increasing length and size of the alkyl function. Among these compounds, AHMA-ethylcarbamate (18) and 4'-methyl-5'-dimethylaminoethylcarboxamido-AHMA-ethylcarbamate (34) possess potent cytotoxicity on the inhibition of human leukemic HL-60 cell growth in culture. Further in vivo studies of these compounds displayed significant anticancer therapeutic effects in mice bearing sarcoma 180, Lewis lung carcinoma, and P388 leukemia.