N-(2-methoxyphenyl)-4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)benzamide | 869474-43-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-methoxyphenyl)-4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)benzamide
• 英文别名: N-(2-Methoxyphenyl)-4-{[3-(4-Oxo-3,4-Dihydroquinazolin-2-Yl)propanoyl]amino}benzamide；N-(2-methoxyphenyl)-4-[3-(4-oxo-3H-quinazolin-2-yl)propanoylamino]benzamide
• CAS: 869474-43-1
• 化学式: C₂₅H₂₂N₄O₄
• 分子量: 442.474
• InChiKey: WWKKOAKRYQQEBT-UHFFFAOYSA-N

物化性质

• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氨基-N-(2-甲氧基苯基)-苯甲酰胺 、 3-(4-氧代-3,4-二氢-2-喹唑啉)-丙酸 在 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-methoxyphenyl)-4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)benzamide
  参考文献：
  名称：

  Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors

  摘要：

  Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting β-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of APC-mutant colorectal cancer. Hit compound 8 was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound 8 leading to the identification of more potent and selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies.

  DOI：

  10.1021/jm401317z

文献信息

• [EN] 1,4-DICARBONYL-PIPERIDYL DERIVATIVES<br/>[FR] DÉRIVÉS DE 1,4-DICARBONYLE-PIPÉRIDYLE
  申请人：MERCK PATENT GMBH

  公开号：WO2017076484A1

  公开（公告）日：2017-05-11

  Compounds of the formula I in which Z, W, Q, R and Y 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.

  式I中Z、W、Q、R和Y具有权利要求1中指示的含义的化合物是坦克酶的抑制剂，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。
• [EN] OXOQUINAZOLINYL-BUTANAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS OXOQUINAZOLINYL-BUTANAMIDE
  申请人：MERCK PATENT GMBH

  公开号：WO2015014442A1

  公开（公告）日：2015-02-05

  Compounds of the formula I in which R1-R3 and Z 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中的化合物，其中R1-R3和Z具有权利要求1中指示的含义，是Tankyrase的抑制剂，可用于治疗癌症、心血管疾病、中枢神经系统损伤以及不同形式的炎症等疾病。
• OXOQUINAZOLINYL-BUTANAMIDE DERIVATIVES
  申请人：MERCK PATENT GMBH

  公开号：US20160184310A1

  公开（公告）日：2016-06-30

  Compounds of the formula I in which R 1 -R 3 and Z 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，其中R1-R3和Z具有声明1中指示的含义，是Tankyrase的抑制剂，可以用于治疗癌症、心血管疾病、中枢神经系统损伤和不同形式的炎症等疾病。
• Antiviral axin stabilizer
  申请人：The Board of Regents for Oklahoma State University

  公开号：US10064862B2

  公开（公告）日：2018-09-04

  Methods and compositions for preventing and/or treating viral infections are provided. The methods involve administering an agent that stabilizes or enhances Axin1 activity, e.g. and agent that inhibits tankyrase. Administration of the agent stimulates or increases interferon activity, thereby preventing or lessening at least one symptom of virus infection. The virus infection may be caused by a respiratory virus such as influenza vims.

  提供了预防和/或治疗病毒感染的方法和组合物。这些方法包括施用稳定或增强 Axin1 活性的制剂，例如抑制 tankyrase 的制剂。给药可刺激或增加干扰素活性，从而预防或减轻病毒感染的至少一种症状。病毒感染可由呼吸道病毒引起，如流感病毒。
• 1,4-dicarbonyl-piperidyl derivatives
  申请人：Merck Patent GmbH

  公开号：US10570116B2

  公开（公告）日：2020-02-25

  Compounds of the formula I in which Z, W, Q, R and Y 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.

  式 I 的化合物 其中 Z、W、Q、R 和 Y 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。