2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one | 878433-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one
• 英文别名: 2-(4-(4-methoxyphenyl)piperazin-1-yl)-5,6,7,8-tetrahydroquinazolin-4(3H)-one；2-[4-(4-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-4(3H)-one；2-[4-(4-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one
• CAS: 878433-57-9
• 化学式: C₁₉H₂₄N₄O₂
• mdl: MFCD06753121
• 分子量: 340.425
• InChiKey: NQWCDPUWUGDETK-UHFFFAOYSA-N

物化性质

• 沸点：
  538.4±60.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-环己酮甲酸乙酯 在 potassium carbonate 作用下， 以 水 、 甲苯 为溶剂， 反应 116.0h， 生成 2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one
  参考文献：
  名称：

  发现新型螺二吲哚啉衍生物作为选择性坦科聚合酶抑制剂。

  摘要：

  经典的WNT途径在癌症发病机理中起重要作用。据报道，抑制端粒聚合酶（TNKS / TNKS2）的聚（ADP-核糖）聚合酶催化活性可通过防止AXIN（Wnt /β的负调节剂）的多聚ADP-核糖基化依赖性降解来降低Wnt /β-catenin信号。 -catenin信号传导。为了研究tankyrase和Wnt途径抑制对肿瘤生长的影响，我们着手寻找具有类似药物性质的TNKS / TNKS2小分子抑制剂。从1a开始，它是一种高通量筛选命中物，螺环丝氨酸衍生物40c（RK-287107）被发现是一种有效的TNKS / TNKS2抑制剂，对PARP1酶的选择性> 7000倍，从而抑制了WNT响应的TCF报道分子的活性和增殖。人结肠直肠癌细胞系COLO-320DM的制备。在小鼠异种移植模型中，RK-287107还显示出剂量依赖性的肿瘤生长抑制作用。这些观察结果表明，RK-287107是一种有前途的先导化

  DOI：

  10.1021/acs.jmedchem.8b01888

文献信息

• TETRAHYDRO-QUINAZOLINONE DERIVATIVES AS TANK AND PARP INHIBITORS
  申请人：MERCK PATENT GMBH

  公开号：US20150025071A1

  公开（公告）日：2015-01-22

  Compounds of the formula I in which U, V and W have the meanings indicated in claim 1 , are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.

  公式I的化合物中，U、V和W的含义如权利要求1所示，是Tankyrase的抑制剂，可用于治疗癌症、心血管疾病、中枢神经系统损伤和不同形式的炎症等疾病。
• USE OF DIANHYDROGALACTITOL OR DERIVATIVES OR ANALOGS THEREOF FOR TREATMENT OF PEDIATRIC CENTRAL NERVOUS SYSTEM MALIGNANCIES
  申请人：DelMar Pharmaceuticals, Inc.

  公开号：US20180071244A1

  公开（公告）日：2018-03-15

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of malignancies of the central nervous system in pediatric patients, including glioblastoma multiforme (GBM) high grade glioma, and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation and that can induce double-stranded breaks in DNA. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents (e.g. cisplatin) and can possess additive or super-additive effects.
• USE OF DIANHYDROGALACTITOL AND DERIVATIVES THEREOF IN THE TREATMENT OF GLIOBLASTOMA, LUNG CANCER, AND OVARIAN CANCER
  申请人：Bacha Jeffrey A.

  公开号：US20190091195A1

  公开（公告）日：2019-03-28

  Substituted hexitol derivatives such as dianhydrogalactitol are useful in the treatment of various neoplastic pathologies. Said pathologies include glioblastoma multiforme, non-small-cell lung carcinoma (NSCLC), ovarian cancer, and leptomeningeal carcinomatosis. The anti-neoplastic activity of dianhydrogalactitol is demonstrated to be due to its activity as an alkylating agent that creates N 7 methylation and inter-strand DNA crosslinks. The hexitol derivatives may be used alone or in combination with other anti-neoplastic agents.
• US9339503B2
  申请人：——

  公开号：US9339503B2

  公开（公告）日：2016-05-17
• [EN] TETRAHYDRO-QUINAZOLINONE DERIVATIVES AS TANK AND PARP INHIBITORS<br/>[FR] DÉRIVÉS TÉTRAHYDRO-QUINAZOLINONE COMME INHIBITEURS DE TANK ET DE PARP
  申请人：MERCK PATENT GMBH

  公开号：WO2013117288A1

  公开（公告）日：2013-08-15

  Compounds of the formula I in which U, V and W have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.