4,5-bis(hydroxymethyl)acridine | 643742-30-7

• 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: 4,5-bis(hydroxymethyl)acridine
• 英文别名: [5-(hydroxymethyl)acridin-4-yl]methanol
• CAS: 643742-30-7
• 化学式: C₁₅H₁₃NO₂
• 分子量: 239.274
• InChiKey: YKAXSYISBLMIQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  53.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5-bis(hydroxymethyl)acridine 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 以51%的产率得到acridine-4,5-dicarbaldehyde
  参考文献：
  名称：

  大环DNA不匹配结合配体：选择性的结构决定因素。

  摘要：

  通过芳族二醛与脂肪族二胺的一步或两步缩合制备了15个同二聚体和5个异二聚体大环双嵌入剂。值得注意的是，异源二聚体支架是首次合成的。通过热变性和荧光嵌入剂置换实验研究了这些大环与含错配胸腺嘧啶残基（TX）的DNA双链体以及完全配对的对照（TA）的结合。双萘衍生物，特别是2,7-二取代的萘衍生物，对TX错配的选择性最高，因为这些大环与完全配对的DNA没有明显的结合。相比之下，其他大环配体以及7种常规DNA结合剂对错配位点的选择性较小或没有。

  DOI：

  10.1002/chem.200901989
• 作为产物：
  描述：

  吖啶 在 硫酸 、 calcium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 4,5-bis(hydroxymethyl)acridine
  参考文献：
  名称：

  吖啶环的反应性：吖啶和一些衍生物的一锅区域选择性单溴甲基化和双溴甲基化

  摘要：

  我们在此报告了 4-溴甲基吖啶和 4,5-双-（溴甲基）吖啶的新的有效区域选择性合成路线，这是用于各种 4-亚甲基吖啶和 4,5-双-（亚甲基）吖啶衍生物的两种有趣的起始材料，在一个用溴甲基甲基醚 (BMME) 直接对吖啶进行溴甲基化。我们还描述了来自相应的 4,5-双（羟甲基）吖啶前体的一些生物学上有趣的二酯衍生物。

  DOI：

  10.1055/s-2003-42104

文献信息

• Reactivity of the Acridine Ring: One-Pot Regioselective Single and Double Bromomethylation of Acridine and Some Derivatives
  作者：Julien Chiron、Jean-Pierre Galy

  DOI：10.1055/s-2003-42104

  日期：——

  here a new efficient regioselective synthetic route to 4-bromomethylacridine and to 4,5-bis-(bromomethyl)acridine, two interesting starting materials for various 4-methyleneacridine and 4,5-bis-(methylene)acridine derivatives, in one step by direct bromomethylation of acridine with bromomethylmethylether (BMME). We also describe some biologically interesting diesters derivatives from the corresponding

  我们在此报告了 4-溴甲基吖啶和 4,5-双-（溴甲基）吖啶的新的有效区域选择性合成路线，这是用于各种 4-亚甲基吖啶和 4,5-双-（亚甲基）吖啶衍生物的两种有趣的起始材料，在一个用溴甲基甲基醚 (BMME) 直接对吖啶进行溴甲基化。我们还描述了来自相应的 4,5-双（羟甲基）吖啶前体的一些生物学上有趣的二酯衍生物。
• Synthesis and biological evaluation of novel 4,5-bis(dialkylaminoalkyl)-substituted acridines as potent telomeric G-quadruplex ligands
  作者：Marie Laronze-Cochard、Young-Min Kim、Bertrand Brassart、Jean-François Riou、Jean-Yves Laronze、Janos Sapi

  DOI：10.1016/j.ejmech.2009.04.021

  日期：2009.10

  Several 4,5-bis(dialkylaminoalkyl)-substituted acridines have been prepared starting from acridine and their telomeric G-quadruplex stabilizing properties were evaluated using FRET melting and TRAP (Telomerase Repeat Amplification Protocol Assay) experiments.

  从a啶开始已制备了几种4,5-双（二烷基氨基烷基）-取代的cr啶，并使用FRET熔解和TRAP（端粒酶重复扩增方案测定）实验评估了它们的端粒G-四链体稳定特性。
• Synthesis of Acridine Analogues as Intercalating Crosslinkers and Evaluation of Their Potential Anticancer Properties
  作者：Toshinori Higashi、Maki Sakamoto、Masataka Mochizuki

  DOI：10.3987/com-08-11346

  日期：——

  We synthesized 4,5-bis(halomethyl)acridines, which contain an acridine skeleton for DNA intercalation and two halomethyl groups for DNA crosslinking. 4,5 -Bis(bromomethyl)acridine and 4,5-bis(chloromethyl)acridine intercalated in DNA and mediated interstrand DNA crosslinking. Both compounds were cytotoxic to CCRF-HSB-2 cells, a human T cell leukemia cell line. Molecular modeling of 4,5-bis(bromomethyl)acridine intercalated in 5'-GC-3' base pairs of DNA indicated that the bromomethyl group, which mediates alkylation, is in close proximity to N7 of guanine.
• Macrocyclic DNA-Mismatch-Binding Ligands: Structural Determinants of Selectivity
  作者：Anton Granzhan、Eric Largy、Nicolas Saettel、Marie-Paule Teulade-Fichou

  DOI：10.1002/chem.200901989

  日期：2010.1.18

  the highest selectivity for the TX mismatches, as these macrocycles show no apparent binding to the fully paired DNA. By contrast, other macrocyclic ligands, as well as seven conventional DNA binders, show lesser or no selectivity for the mismatch sites. The study demonstrates that the topology of the ligands plays a crucial role in determining the mismatch‐binding affinity and selectivity of the macrocyclic

  通过芳族二醛与脂肪族二胺的一步或两步缩合制备了15个同二聚体和5个异二聚体大环双嵌入剂。值得注意的是，异源二聚体支架是首次合成的。通过热变性和荧光嵌入剂置换实验研究了这些大环与含错配胸腺嘧啶残基（TX）的DNA双链体以及完全配对的对照（TA）的结合。双萘衍生物，特别是2,7-二取代的萘衍生物，对TX错配的选择性最高，因为这些大环与完全配对的DNA没有明显的结合。相比之下，其他大环配体以及7种常规DNA结合剂对错配位点的选择性较小或没有。
• Synthesis and antileishmanial activities of 4,5-di-substituted acridines as compared to their 4-mono-substituted homologues
  作者：Di Giorgio Carole、De Méo Michel、Chiron Julien、Delmas Florence、Nikoyan Anna、Jean Séverine、Dumenil Gérard、Timon-David Pierre、Galy Jean-Pierre

  DOI：10.1016/j.bmc.2005.06.045

  日期：2005.10

  Newly synthesized 4,5-di-substituted acridines were assessed for in vitro antileishmanial activities as compared to those of their 4-mono-substituted homologues. Mono-substituted acridines exhibited a weak specificity for Leishmania parasites. Di-substituted acridines, on the contrary, displayed interesting amastigote-specific activities through a mechanism of action that might not involve intercalation to DNA. This antileishmanial property, associated with a low antiproliferative activity towards human cells, led to the identification of a new class of promising acridine derivatives such as 4,5-bis(hydroxymethyl)acridine with a nonclassical mechanism of action based on the inhibition of Leishmania internalization within macrophages. In the meantime, the effects of experimental lighting on the biological properties of acridines were assessed: experimental lighting did not significantly improve the antileishmanial activity of the compounds since it produced a greater toxicity against human cells. (c) 2005 Elsevier Ltd. All rights reserved.