N-(trans-4-(4-cyanophenoxy)cyclohexyl)-3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanamide | 1507362-06-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(trans-4-(4-cyanophenoxy)cyclohexyl)-3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanamide
• CAS: 1507362-06-2
• 化学式: C₂₄H₂₄N₄O₃S
• 分子量: 448.546
• InChiKey: MCMCBDOVNWSRNM-UAPYVXQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  107.87
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  tert-butyl 3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanoate 在 1-丙基磷酸酐 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-(trans-4-(4-cyanophenoxy)cyclohexyl)-3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanamide
  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] QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF<br/>[FR] COMPOSÉS QUINAZOLINONES ET LEURS DÉRIVÉS
  申请人：AMGEN INC

  公开号：WO2014036022A1

  公开（公告）日：2014-03-06

  Compounds of Formula I are useful inhibitors of tankyrase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物是坦克酶的有用抑制剂。公式I的化合物具有以下结构：其中变量的定义在此提供。
• Quinazolinone Compounds and Derivatives Thereof
  申请人：AMGEN INC.

  公开号：US20150225396A1

  公开（公告）日：2015-08-13

  Compounds of Formula I are useful inhibitors of tankyrase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物是坦克酰酶的有用抑制剂。公式I的化合物具有以下结构：其中变量的定义在此提供。
• 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。
• Methods for treating diseases related to the wnt pathway
  申请人：Sandia Corporation

  公开号：US10624949B1

  公开（公告）日：2020-04-21

  The present invention relates to methods for treating a disease, in which the disease arises from dysregulation of the Wnt signaling pathway. In some instances, the disease can be treated by administering a Wnt pathway inhibitory compound. In other instances, the method optionally includes conducting a genome-wide screening to determine one or more genes resulting in a reduced disease state and then identifying the gene(s) as being involved in the Wnt signaling pathway.

  本发明涉及治疗疾病的方法，其中疾病是由 Wnt 信号通路失调引起的。在某些情况下，可以通过施用抑制 Wnt 通路的化合物来治疗疾病。在其他情况下，该方法可选地包括进行全基因组筛选，以确定导致疾病状态降低的一个或多个基因，然后确定这些基因参与Wnt信号通路。
• QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF
  申请人：AMGEN, INC.

  公开号：EP2890696A1

  公开（公告）日：2015-07-08