(9-chloroacridin-4-yl)-(4-methylpiperazin-1-yl)methanone | 902760-09-2

• 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-chloroacridin-4-yl)-(4-methylpiperazin-1-yl)methanone
• CAS: 902760-09-2
• 化学式: C₁₉H₁₈ClN₃O
• 分子量: 339.824
• InChiKey: DMRDVCCRZGEBTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  24.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  36.44
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (9-chloroacridin-4-yl)-(4-methylpiperazin-1-yl)methanone 在 氨 作用下， 以 various solvent(s) 为溶剂， 生成 (9-Aminoacridin-4-yl)-(4-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  潜在的抗肿瘤药。43.新型抗肿瘤药二元9-氨基ac啶-4-羧酰胺的合成及生物活性。

  摘要：

  报道了新型抗肿瘤剂N- [2-（二烷基氨基）乙基] -9-氨基ac啶-4-羧酰胺的代表的合成和生物学活性。这类成员是稳定的并且非常易溶于水，具有高水平的体外和体内抗肿瘤活性。这些化合物通过插入与双链DNA紧密结合，但对抗肿瘤活性的要求更为严格。它们主要取决于两个阳离子中心的分离距离，位置和pKa值。对于体内活性，对于C-9 a啶位置附近的亲脂性但不存在亲水性基团以及侧链阳离子部分上的亲脂性和亲水性基团存在显着的体积耐受性。侧链阳离子中心pKa的显着减弱消除了活性，

  DOI：

  10.1021/jm00377a017
• 作为产物：
  描述：

  4-羧基-9-茚酮 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 (9-chloroacridin-4-yl)-(4-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  潜在的抗肿瘤药。43.新型抗肿瘤药二元9-氨基ac啶-4-羧酰胺的合成及生物活性。

  摘要：

  报道了新型抗肿瘤剂N- [2-（二烷基氨基）乙基] -9-氨基ac啶-4-羧酰胺的代表的合成和生物学活性。这类成员是稳定的并且非常易溶于水，具有高水平的体外和体内抗肿瘤活性。这些化合物通过插入与双链DNA紧密结合，但对抗肿瘤活性的要求更为严格。它们主要取决于两个阳离子中心的分离距离，位置和pKa值。对于体内活性，对于C-9 a啶位置附近的亲脂性但不存在亲水性基团以及侧链阳离子部分上的亲脂性和亲水性基团存在显着的体积耐受性。侧链阳离子中心pKa的显着减弱消除了活性，

  DOI：

  10.1021/jm00377a017

文献信息

• Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity
  作者：John R. Goodell、Avni A. Madhok、Hiroshi Hiasa、David M. Ferguson

  DOI：10.1016/j.bmc.2006.04.044

  日期：2006.8

  of topoisomerase activity to gain insight into the mechanism of action. The results indicate that the acridine analogs bearing substituted carboxamides and bulky 9-amino functionalities are able to inhibit herpes infections as well as inhibit topoisomerase II relaxation of supercoiled DNA. Given the mechanism of action of amsacrine (a closely related, well-studied 9-amino substituted acridine), the compounds

  对于新的非核苷类抗病毒化合物的发现在治疗疱疹病毒感染方面具有重要意义，并且受到越来越多的关注，因为出现了核苷抗性菌株。使用全细胞病毒诱导的细胞致病性分析，我们测试了一系列取代的三芳基杂环化合物，包括a啶酮，x吨酮和a啶。进一步显示出对单纯疱疹-1和/或单纯疱疹2具有活性的化合物对拓扑异构酶活性的抑制作用，以深入了解其作用机理。结果表明，带有取代的羧酰胺和庞大的9-氨基官能团的the啶类似物能够抑制疱疹感染以及抑制超螺旋DNA的拓扑异构酶II松弛。鉴于氨苄青霉素的作用机理（密切相关，研究充分的9-氨基取代a啶），进一步在DNA拓扑异构酶II裂解试验中测试化合物，以确定化合物是否具有毒性。结果表明，在这项研究中合成的a啶通过与氨s碱不同的机制起作用，很可能是通过阻断拓扑异构酶与DNA的结合（类似于阿克拉比星）。这不仅表明治疗疱疹病毒感染的独特作用机制，而且对靶向拓扑异构酶II活性的抗癌药的开发
• Identification of Compounds with Anti-West Nile Virus Activity
  作者：John R. Goodell、Francesc Puig-Basagoiti、Brett M. Forshey、Pei-Yong Shi、David M. Ferguson

  DOI：10.1021/jm051229y

  日期：2006.3.1

  The lack of antiviral compounds targeting flaviviruses represents a significant problem in the development of strategies for treating West Nile Virus (WNV), Dengue, and Yellow Fever infections. Using WNV high-throughput screening techniques developed in Our laboratories, we report the identification of several small molecule anti-WNV compounds belonging to four different structural classes including pyrazolines, xanthanes, acridines, and quinolines. The initial set of "hits" was further refined using cell viability-cytotoxicity assays to two 1,3,5-triaryl pyrazoline compounds: 1-(4-chlorophenylacetyl)-5-(4-nitrophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole and 1-benzoyl-5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole. On the basis of their activity and favorable therapeutic indexes, these compounds were identified as viable leads and subjected to additional evaluation using an authentic viral titer reduction assay employing an epidemic strain of WNV. The compounds were further evaluated in a transient replicon reporting system to gain insight into the mechanism of action by identifying the step at which inhibition takes place during viral replication. The results indicate the pyrazolines inhibit RNA synthesis, pointing to viral RNA polymerase, RNA helicase, or other viral replication enzymes as potential targets. Progress was also made in understanding the structural requirements for activity by synthesizing a focused chemical library of substituted pyrazolines. Preliminary SAR data are presented that show the aryl-rings are required for activity against WNV. More importantly, the results indicate WNV activity is tolerant to aryl-substitutions paving the way for the design and development of much larger combinatorial libraries with varied physicochemical properties.
• Synthesis and evaluation of 9-aminoacridines derived from benzyne click chemistry
  作者：Lesley A. Howell、Aaron Howman、Maria A. O’Connell、Anja Mueller、Mark Searcey

  DOI：10.1016/j.bmcl.2009.08.070

  日期：2009.10

  A small set of 9-aminoacridine-3- and 4-carboxamides were synthesized efficiently using the benzyne/azide click chemistry. The products bind to duplex DNA but have different antitumour activity in the HL60 cell line. (C) 2009 Elsevier Ltd. All rights reserved.
• ATWELL, G. A.;CAIN, B. F.;BAGULEY, B. C.;FINLAY, G. J.;DENNY, W. A., J. MED. CHEM., 1984, 27, N 11, 1481-1485
  作者：ATWELL, G. A.、CAIN, B. F.、BAGULEY, B. C.、FINLAY, G. J.、DENNY, W. A.

  DOI：——

  日期：——