[2-(4-aminophenyl)ethyl]-(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-amine | 1192752-15-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: [2-(4-aminophenyl)ethyl]-(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-amine
• 英文别名: N-[2-(4-aminophenyl)ethyl]-5,6-diphenylfuro[2,3-d]pyrimidin-4-amine；N-(4-aminophenethyl)-5,6-diphenylfuro[2,3-d]pyrimidin-4-amine
• CAS: 1192752-15-0
• 化学式: C₂₆H₂₂N₄O
• 分子量: 406.487
• InChiKey: BHSCMKZMALDDCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-(4-aminophenyl)ethyl]-(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-amine 在 碳酸氢钠 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 8.17h， 生成 1-(4-{2-[(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)amino]ethyl}phenyl)-3-(5-methyl-1H-pyrazol-3-yl)urea
  参考文献：
  名称：

  双重FLT3–Aurora A抑制剂的简便鉴定：计算机辅助药物设计方法

  摘要：

  计算机指导的药物设计是药物发现的强大工具。本文中，我们公开了使用这种方法来发现双重FMS样受体酪氨酸激酶3（FLT3）– Aurora A抗癌抑制剂。选择了一个极光命中化合物作为起点，从中筛选了288个虚拟分子。随后，合成了其中一些化合物，并评估了它们抑制FLT3和Aurora激酶A的能力。为了进一步增强FLT3抑制作用，通过简化策略和生物等位取代对先导化合物进行了结构-活性关系研究，然后使用计算机引导的药物设计，可根据有利的结合能对带有各种不同末端基团的分子进行优先排序。然后合成选定的化合物，并评估其生物活性。这些，50的7 n M值。因此，它被认为是进一步发展的极有希望的候选者。

  DOI：

  10.1002/cmdc.201300571
• 作为产物：
  描述：

  4-氯-5,6-二苯基呋喃并[2,3-D]嘧啶 、 2-(4-氨基苯)乙胺 在 水 、 乙酸乙酯 、 crude compound 、 silica gel 、 methanol-dichloromethane 作用下， 以 正丁醇 为溶剂， 反应 16.0h， 以to give N-(4-aminophenethyl)-5,6-diphenylfuro[2,3-d]pyrimidin-4-amine (0.195 g, 74%)的产率得到[2-(4-aminophenyl)ethyl]-(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-amine
  参考文献：
  名称：

  FUSED BICYCLIC PYRIMIDINE COMPOUNDS AS AURORA KINASE INHIBITORS

  摘要：

  公式（I）的融合双环嘧啶化合物：其中R1，R3，R4，X1，X2，Y，Z，A，B，C，D，n和两个键在此定义。还披露了一种抑制Aurora激酶活性的方法和一种使用这些化合物治疗癌症的方法。

  公开号：

  US20090275533A1

文献信息

• Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
  申请人：National Health Research Institutes

  公开号：US08138194B2

  公开（公告）日：2012-03-20

  Fused bicyclic pyrimidine compounds of formula (I): wherein R1, R3, R4, X1, X2, Y, Z, A, B, C, D, n, and the two bonds are defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds.

  式(I)的融合双环嘧啶化合物：其中R1、R3、R4、X1、X2、Y、Z、A、B、C、D、n和两个键在此定义。还公开了一种抑制极化激酶活性的方法和一种使用这些化合物治疗癌症的方法。
• Fast-Forwarding Hit to Lead: Aurora and Epidermal Growth Factor Receptor Kinase Inhibitor Lead Identification
  作者：Mohane Selvaraj Coumar、Chang-Ying Chu、Cheng-Wei Lin、Hui-Yi Shiao、Yun-Lung Ho、Randheer Reddy、Wen-Hsing Lin、Chun-Hwa Chen、Yi-Hui Peng、Jiun-Shyang Leou、Tzu-Wen Lien、Chin-Ting Huang、Ming-Yu Fang、Szu-Huei Wu、Jian-Sung Wu、Santhosh Kumar Chittimalla、Jen-Shin Song、John T.-A. Hsu、Su-Ying Wu、Chun-Chen Liao、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1021/jm1000198

  日期：2010.7.8

  A focused library of furanopyrimidine (350 compounds) was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit la was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity in HCT-116 colon cancer cell line. On the basis of docking studies with EGFR hit Is, introduction of acrylamide Michael acceptor group led to 8, which inhibited both the wild and mutant EGFR kinase and also showed antiproliferative activity in HCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.
• Optimization of Ligand and Lipophilic Efficiency To Identify an in Vivo Active Furano-Pyrimidine Aurora Kinase Inhibitor
  作者：Hui-Yi Shiao、Mohane Selvaraj Coumar、Chun-Wei Chang、Yi-Yu Ke、Ya-Hui Chi、Chang-Ying Chu、Hsu-Yi Sun、Chun-Hwa Chen、Wen-Hsing Lin、Ka-Shu Fung、Po-Chu Kuo、Chin-Ting Huang、Kai-Yen Chang、Cheng-Tai Lu、John T. A. Hsu、Chiung-Tong Chen、Weir-Torn Jiaang、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1021/jm4006059

  日期：2013.7.11

  Ligand efficiency (LE) and lipophilic efficiency (LipE) are two important indicators of "drug-likeness", which are dependent on the molecules activity and physicochemical properties. We recently reported a furano-pyrimidine Aurora kinase inhibitor 4 (LE = 0.25; LipE = 1.75), with potent activity in vitro; however, 4 was inactive in vivo. On the basis of insights obtained from the X-ray co-crystal structure of the lead 4, various solubilizing functional groups were introduced to optimize both the activity and physicochemical properties. Emphasis was placed on identifying potential leads with improved activity as well as better LE and LipE by exercising tight control over the molecular weight and lipophilicity of the molecules. Rational optimization has led to the identification of Aurora kinase inhibitor 27 (IBPR001; LE = 0.26; LipE = 4.78), with improved in vitro potency and physicochemical properties, resulting in an in vivo active (HCT-116 colon cancer xenograft mouse model) anticancer agent.
• US8138194B2
  申请人：——

  公开号：US8138194B2

  公开（公告）日：2012-03-20
• [EN] FUSED BICYCLIC PYRIMIDINE COMPOUNDS AS AURORA KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRIMIDINE BICYCLIQUES FUSIONNÉS EN TANT QU'INHIBITEURS D'AURORA KINASE
  申请人：NAT HEALTH RESEARCH INSTITUTES

  公开号：WO2009134658A2

  公开（公告）日：2009-11-05

  Fused bicyclic pyrimidine compounds of formula (I) defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds.