1-{4-[(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)amino]-phenyl}-3-phenylurea | 1446023-11-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: 1-{4-[(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)amino]-phenyl}-3-phenylurea
• 英文别名: 1-[4-[(5,6-Diphenylfuro[2,3-d]pyrimidin-4-yl)amino]phenyl]-3-phenylurea；1-[4-[(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)amino]phenyl]-3-phenylurea
• CAS: 1446023-11-5
• 化学式: C₃₁H₂₃N₅O₂
• 分子量: 497.556
• InChiKey: HMEFOYWOEZKPAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)benzene-1,4-diamine 、 异氰酸苯酯 以 二氯甲烷 为溶剂， 反应 8.0h， 以73%的产率得到1-{4-[(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)amino]-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

• 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.