trans-methyl 4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)cyclohexane carboxylate | 1507362-23-3

• 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: trans-methyl 4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)cyclohexane carboxylate
• CAS: 1507362-23-3
• 化学式: C₁₉H₂₃N₃O₄
• 分子量: 357.409
• InChiKey: SXXDYJMDRMFJNR-JOCQHMNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  101.15
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  trans-methyl 4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)cyclohexane carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以100%的产率得到trans-4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)cyclohexane carboxylic acid
  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：

  methyl trans-4-aminocyclohexanecarboxylate hydrochloride 、 3-(4-氧代-3,4-二氢-2-喹唑啉)-丙酸 在 N,N-二异丙基乙胺 、 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， 以48.7%的产率得到trans-methyl 4-(3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanamido)cyclohexane carboxylate
  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

• 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。
• US9505749B2
  申请人：——

  公开号：US9505749B2

  公开（公告）日：2016-11-29