4-(1-(4-methoxybenzyl)-5-amino-1H-imidazol-4-yl)-1-(4-methoxybenzyl)-5-imino-1H-imidazol-2(5H)-one | 1070773-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(1-(4-methoxybenzyl)-5-amino-1H-imidazol-4-yl)-1-(4-methoxybenzyl)-5-imino-1H-imidazol-2(5H)-one
• 英文别名: 4-[5-Amino-1-[(4-methoxyphenyl)methyl]imidazol-4-yl]-5-imino-1-[(4-methoxyphenyl)methyl]imidazol-2-one
• CAS: 1070773-13-5
• 化学式: C₂₂H₂₂N₆O₃
• 分子量: 418.455
• InChiKey: PYPXRCUYPJVCBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(1-(4-methoxybenzyl)-5-amino-1H-imidazol-4-yl)-1-(4-methoxybenzyl)-5-imino-1H-imidazol-2(5H)-one 、 均苯四甲酸二酐 在 硫酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以46%的产率得到3,7-dihydro-3,7-bis[(4-methoxyphenyl)methyl]-5-(2,4,5-tricarboxyphenyl)-2H-diimidazo[4,5-d:4',5'-f][1,3]diazepin-2-one
  参考文献：
  名称：

  包含三环5：7：5-融合二咪唑二氮杂卓环系统的新型广谱抗癌药。

  摘要：

  报道了一系列新颖的，广谱的抗癌药，其中包含三环5：7：5-稠合的二咪唑并[4,5-d：4'，5'-f] [1,3]二氮杂ze环系统。该系列中的化合物1、2、8、11和12显示出有希望的体外抗肿瘤活性，且低微摩尔IC（50）对前列腺癌，肺癌，乳腺癌和卵巢癌细胞系具有抗性。提出了一些关于构效关系和生物活性可能机制的概念。还介绍了使用SCID小鼠对1的初步体内毒性研究。

  DOI：

  10.1021/ml100281b
• 作为产物：
  描述：

  5-amino-1-[(4-methoxyphenyl)methyl]-N-[(4-methoxyphenyl)methylcarbamoyl]imidazole-4-carboximidoyl cyanide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 4-(1-(4-methoxybenzyl)-5-amino-1H-imidazol-4-yl)-1-(4-methoxybenzyl)-5-imino-1H-imidazol-2(5H)-one
  参考文献：
  名称：

  Structure-based drug design and potent anti-cancer activity of tricyclic 5:7:5-fused diimidazo[4,5-d:4′,5′-f][1,3]diazepines

  摘要：

  Judicial structural modifications of 5: 7-fused ring-expanded nucleosides (RENs), based on molecular modeling studies with one of its known targets, human RNA helicase (hDDX3), led to the lead, novel, 5:7-5-fused tricyclic heterocycle (1). The latter exhibited promising broad-spectrum in vitro anti-cancer activity against a number of cancer cell lines screened. This paper describes our systematic, albeit limited, structure-activity relationship (SAR) studies on this lead compound, which produced a number of analogs with broad-spectrum in vitro anti-cancer activities against lung, breast, prostate, and ovarian cancer cell lines, in particular compounds 15i, 15j, 15m and 15n which showed IC50 values in submicromolar to micromolar range, and are worthy of further explorations. The SAR data also enabled us to propose a tentative SAR model for future SAR efforts for ultimate realization of optimally active and minimally toxic anti-cancer compounds based on the diimidazo[4,5-d:4',5'-f][1,3]diazepine structural skeleton of the lead compound 1. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.050

文献信息

• The First Synthesis of a Novel 5:7:5-Fused Diimidazodiazepine Ring System and Some of Its Chemical Properties
  作者：Raj Kumar、Ravi K. Ujjinamatada、Ramachandra S. Hosmane

  DOI：10.1021/ol8020176

  日期：2008.10.16

  The first synthesis of a novel 5:7:5-fused heterocyclic ring system, a diimidazodiazepine, is reported. The propensity of the ring system to undergo facile, acid-catalyzed nucleophilic addition reactions by neutral carbon and nitrogen nucleophiles has been explored. The ring system has potential future applications in mechanistic studies of formation and repair of DNA interstrand cross-links.

  报道了新颖的5：7：5-稠合杂环系统，二咪唑并二氮杂pine的首次合成。已经探索了环系统易于通过中性碳和氮亲核试剂进行酸催化的亲核加成反应的倾向。该环系统在DNA链间交联的形成和修复机理研究中具有潜在的未来应用。
• Fused Diimidazodiazepine Compounds and Methods of Use and Manufacture Thereof
  申请人：Hosmane Ramachandra S.

  公开号：US20110275588A1

  公开（公告）日：2011-11-10

  The invention encompasses novel compounds and pharmaceutically acceptable salts thereof and compositions including therapeutically or prophylactically effective amounts of such compounds or pharmaceutically acceptable salts thereof. The invention also encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, which methods include administering to a mammal in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof.

  本发明涵盖了新型化合物及其药学上可接受的盐和包含这些化合物或其药学上可接受的盐的治疗或预防有效量的组合物。本发明还涵盖了用于治疗或预防与异常细胞生长相关的疾病和疾病的方法，例如，治疗或预防癌症或肿瘤生长的方法，其中包括向需要治疗的哺乳动物投与本发明化合物或其药学上可接受的盐的治疗或预防有效量的组合物。
• [EN] FUSED DIIMIDAZODIAZEPINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE THEREOF<br/>[FR] COMPOSÉS DIIMIDAZODIAZÉPINE FUSIONNÉS ET LEURS MÉTHODES D'UTILISATION ET DE FABRICATION
  申请人：UNIV MARYLAND

  公开号：WO2010039187A3

  公开（公告）日：2010-06-17
• FUSED DIIMIDAZODIAZEPINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE THEREOF
  申请人：The Johns Hopkins University

  公开号：EP2350086B1

  公开（公告）日：2021-04-21
• DDX3 AS A BIOMARKER FOR CANCER AND METHODS RELATED THERETO
  申请人：The Johns Hopkins University

  公开号：US20130281440A1

  公开（公告）日：2013-10-24

  The invention encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, by administering to a subject in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound that downregulates DDX3, for example a fused diimidazodiazepine ring compound or a pharmaceutically acceptable salt thereof. The invention also encompasses the use of DDX3 as a biomarker for diagnostic and treatment purposes, for example, to identify a hyperproliferative disorder susceptible to treatment by down regulation of DDX3.