3,6-bis(3-chloropropionamido)acridine | 250256-09-8

• 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: 3,6-bis(3-chloropropionamido)acridine
• 英文别名: 3-chloro-N-[6-(3-chloropropanoylamino)acridin-3-yl]propanamide
• CAS: 250256-09-8
• 化学式: C₁₉H₁₇Cl₂N₃O₂
• 分子量: 390.269
• InChiKey: NQISYJRVQHOCAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  七亚甲基亚胺 、 3,6-bis(3-chloropropionamido)acridine 在 sodium iodide 作用下， 以 乙醇 为溶剂， 生成 3,6-bis[3-(heptamethyleneimino)propionamido]acridine
  参考文献：
  名称：

  Human telomerase inhibition by substituted acridine derivatives

  摘要：

  A series of 3,6-disubstituted acridine derivatives have been rationally designed as telomerase inhibitors. They have been designed on the basis that inhibition of telomerase occurs by stabilising G-quadruplex structures formed by the folding of telomeric DNA. The most potent inhibitors have IC50 values against telomerase of between 1.3 and 8 mu M, comparable to their cytotoxicity in ovarian cancer cell lines. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00394-7
• 作为产物：
  描述：

  原黄素 、 3-氯丙酰氯 反应 3.0h， 以90%的产率得到3,6-bis(3-chloropropionamido)acridine
  参考文献：
  名称：

  Fluorine in medicinal chemistry: β-fluorination of peripheral pyrrolidines attached to acridine ligands affects their interactions with G-quadruplex DNA

  摘要：

  比较X射线结构研究表明，在G-四链体DNA结合配体BSU6039的吡咯烷外围部分中引入C-F键，与非氟化类似物相比，会导致吡咯烷环构象发生明显变化，并产生不同的结合模式，其中涉及吡咯烷N+—H取向的逆转。

  DOI：

  10.1039/c0ob00886a

文献信息

• Molecular Modeling Studies on G-Quadruplex Complexes of Telomerase Inhibitors:  Structure−Activity Relationships
  作者：Martin A. Read、Alexis A. Wood、John R. Harrison、Sharon M. Gowan、Lloyd R. Kelland、Harvinder S. Dosanjh、Stephen Neidle

  DOI：10.1021/jm990287e

  日期：1999.11.1

  Inhibition of the ability of the enzyme telomerase to add telomeric repeats to the end of chromosomes is a novel target for potential anticancer therapy. This paper examines the hypothesis that compounds possessing a planar aromatic chromophore inhibit telomerase via stabilization of, and binding to, a folded guanine quadruplex structure. Two series of telomerase inhibitors have been designed based on the 2,6-disubstituted amidoanthracene-9,10-dione and a,6-disubstituted acridine chromophores in order to investigate structure-activity relationships between biological activity and substituent group size. The relative binding energies between these compounds and the folded human telomere DNA quadruplex were determined using molecular simulation methods, involving explicitly solvated structures. The results obtained are in excellent agreement with the biological activity as measured in vitro using a modified TRAP assay and in general agreement with the ranking order of binding enthalpies found in isothermal titration calorimetry studies. This broad agreement provides strong support for the hypothesis that guanine quadruplexes are the primary target for telomerase inhibitors with extended planar chromophores.
• Human telomerase inhibition by substituted acridine derivatives
  作者：R. John Harrison、Sharon M. Gowan、Lloyd R. Kelland、Stephen Neidle

  DOI：10.1016/s0960-894x(99)00394-7

  日期：1999.9

  A series of 3,6-disubstituted acridine derivatives have been rationally designed as telomerase inhibitors. They have been designed on the basis that inhibition of telomerase occurs by stabilising G-quadruplex structures formed by the folding of telomeric DNA. The most potent inhibitors have IC50 values against telomerase of between 1.3 and 8 mu M, comparable to their cytotoxicity in ovarian cancer cell lines. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Fluorine in medicinal chemistry: β-fluorination of peripheral pyrrolidines attached to acridine ligands affects their interactions with G-quadruplex DNA
  作者：Nancy H. Campbell、Daniel L. Smith、Anthony P. Reszka、Stephen Neidle、David O'Hagan

  DOI：10.1039/c0ob00886a

  日期：——

  Comparative X-ray structure studies reveal that C–F bond incorporation into the peripheral pyrrolidine moieties of the G-quadruplex DNA binding ligand BSU6039 leads to a distinct pyrrolidine ring conformation, relative to the non-fluorinated analogue, and with a different binding mode involving reversal of the pyrrolidinium N+–H orientation.

  比较X射线结构研究表明，在G-四链体DNA结合配体BSU6039的吡咯烷外围部分中引入C-F键，与非氟化类似物相比，会导致吡咯烷环构象发生明显变化，并产生不同的结合模式，其中涉及吡咯烷N+—H取向的逆转。