1-(4-{2-[(6-{4-[2-(dimethylamino)ethoxy]phenyl}furo[2,3-d]pyrimidin-4-yl)amino]ethyl}phenyl)-3-phenylurea | 1192754-03-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-{2-[(6-{4-[2-(dimethylamino)ethoxy]phenyl}furo[2,3-d]pyrimidin-4-yl)amino]ethyl}phenyl)-3-phenylurea
• 英文别名: 1-[4-[2-[[6-[4-[2-(dimethylamino)ethoxy]phenyl]furo[2,3-d]pyrimidin-4-yl]amino]ethyl]phenyl]-3-phenylurea
• CAS: 1192754-03-2
• 化学式: C₃₁H₃₂N₆O₃
• 分子量: 536.633
• InChiKey: GJFJLQXYFZSVOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-{2-[(6-{4-[2-(dimethylamino)ethoxy]phenyl}furo[2,3-d]pyrimidin-4-yl)amino]ethyl}phenyl)-3-phenylurea 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 1-(4-{2-[(6-{4-[2-(dimethylamino)ethoxy]phenyl}furo[2,3-d]pyrimidin-4-yl)amino]ethyl}phenyl)-3-phenylurea hydrochloride
  参考文献：
  名称：

  Optimization of Ligand and Lipophilic Efficiency To Identify an in Vivo Active Furano-Pyrimidine Aurora Kinase Inhibitor

  摘要：

  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.

  DOI：

  10.1021/jm4006059
• 作为产物：
  描述：

  2-(4-氨基苯)乙胺 在 三溴化硼 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 19.0h， 生成 1-(4-{2-[(6-{4-[2-(dimethylamino)ethoxy]phenyl}furo[2,3-d]pyrimidin-4-yl)amino]ethyl}phenyl)-3-phenylurea
  参考文献：
  名称：

  Optimization of Ligand and Lipophilic Efficiency To Identify an in Vivo Active Furano-Pyrimidine Aurora Kinase Inhibitor

  摘要：

  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.

  DOI：

  10.1021/jm4006059

文献信息

• FUSED BICYCLIC PYRIMIDINE COMPOUNDS AS AURORA KINASE INHIBITORS
  申请人：Hsieh Hsing-Pang

  公开号：US20090275533A1

  公开（公告）日：2009-11-05

  Fused bicyclic pyrimidine compounds of formula (I): wherein R 1 , R 3 , R 4 , X 1 , X 2 , 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和两个键在此处定义。还公开了一种抑制极化激酶活性的方法以及使用这些化合物治疗癌症的方法。
• 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.
• 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.