trans-4-(pyridin-4-yloxy)cyclohexanamine | 872575-60-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: trans-4-(pyridin-4-yloxy)cyclohexanamine
• CAS: 872575-60-5
• 化学式: C₁₁H₁₆N₂O
• 分子量: 192.261
• InChiKey: KOPZKNIPFUAFAM-MGCOHNPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  14.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  48.14
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  trans-4-(pyridin-4-yloxy)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-(pyridin-4-yloxy)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

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。
• Urea derivative and use therefor
  申请人：Toray Industries, Inc.

  公开号：US10280145B2

  公开（公告）日：2019-05-07

  A compound has inhibitory activity on Discoidin Domain Receptor 1. A urea derivative is represented by the formula (I) or a pharmaceutically acceptable salt thereof: wherein, R1 is trifluoromethyl, trifluoromethoxy, or pentafluorosulfanyl; each R2 is independently a hydrogen atom or methyl which is optionally substituted by one hydroxyl or one saturated heterocyclyl having four to six ring-forming atoms; R3 is a hydrogen atom, halogen atom, C1-C3 alkyl, saturated heterocyclyl having four to six ring-forming atoms and optionally having an oxo group, or R5O—; and R4 is phenyl, pyridyl, pyridazinyl, or pyrimidinyl, which phenyl, pyridyl, pyridazinyl, or pyrimidinyl is optionally substituted by one R6.

  一种化合物对 Discoidin Domain Receptor 1 具有抑制活性。脲衍生物由式（I）或其药学上可接受的盐表示： 其中，R1 是三氟甲基、三氟甲氧基或五氟硫酰基；每个 R2 独立地是氢原子或甲基，可选择被一个羟基或一个具有四至六个成环原子的饱和杂环基取代；R3 是氢原子、卤素原子、C1-C3 烷基、具有四至六个成环原子且可选具有一个氧代基团的饱和杂环基，或 R5O-；以及 R4 是苯基、吡啶基、哒嗪基或嘧啶基，其中苯基、吡啶基、哒嗪基或嘧啶基可选被一个 R6 取代。
• UREA DERIVATIVE AND USE THEREFOR
  申请人：Toray Industries, Inc.

  公开号：EP3345893B1

  公开（公告）日：2019-10-30
• QUINAZOLINONE COMPOUNDS AND DERIVATIVES THEREOF
  申请人：AMGEN, INC.

  公开号：EP2890696A1

  公开（公告）日：2015-07-08