3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanoic acid | 313233-21-5

• 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: 3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanoic acid
• 英文别名: 3-(4-Oxo-1,4-dihydro-quinazolin-2-ylsulfanyl)-propionic acid；3-[(4-oxo-3H-quinazolin-2-yl)sulfanyl]propanoic acid
• CAS: 313233-21-5
• 化学式: C₁₁H₁₀N₂O₃S
• mdl: MFCD03560375
• 分子量: 250.278
• InChiKey: JXTBIXJKHMVXHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  (1r,4r)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexanamine 、 3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanoic acid 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)-N-(trans-4-(5-phenyl-1,3,4-oxadiazol-2-yl)cyclohexyl)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
• 作为产物：
  描述：

  tert-butyl 3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以97%的产率得到3-((4-oxo-3,4-dihydroquinazolin-2-yl)thio)propanoic acid
  参考文献：
  名称：

  [EN] QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF
  [FR] COMPOSÉS QUINAZOLINONES ET LEURS DÉRIVÉS

  摘要：

  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。

  公开号：

  WO2014036022A1

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。
• From PARP1 to TNKS2 Inhibition: A Structure-Based Approach
  作者：Stefano Tomassi、Julian Pfahler、Nicola Mautone、Annarita Rovere、Chiara Esposito、Daniela Passeri、Roberto Pellicciari、Ettore Novellino、Martin Pannek、Clemens Steegborn、Alessandro Paiardini、Antonello Mai、Dante Rotili

  DOI：10.1021/acsmedchemlett.9b00654

  日期：2020.5.14

  Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/beta-catenin pathway-dependent solid tumors. Previously, we reported the 2-mercaptoquinazolin-4-one MC2050 as a micromolar PARP1 inhibitor. Here we show how the resolution of the X-ray structure of PARP1 in complex with MC2050, combined with the computational investigation of the structural differences between TNKSs and PARP1 /2 active sites, provided the rationale for a structure-based drug design campaign that with a limited synthetic effort led to the discovery of the bis-quinazolinone 5 as a picomolar and selective TNKS2 inhibitor, endowed with antiproliferative effects in a colorectal cancer cell line (DLD-1) where the Wnt pathway is constitutively activated.
• QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF
  申请人：AMGEN, INC.

  公开号：EP2890696A1

  公开（公告）日：2015-07-08
• COMPOUNDS THAT INHIBIT HUMAN DNA LIGASES AND METHODS OF TREATING CANCER
  申请人：TOMKINSON Alan E.

  公开号：US20100099683A1

  公开（公告）日：2010-04-22

  Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.