(5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-[2-(1H-imidazol-4-yl)-ethyl]amine | 1235310-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: (5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-[2-(1H-imidazol-4-yl)-ethyl]amine
• 英文别名: N-[2-(1H-imidazol-5-yl)ethyl]-5,6-diphenylfuro[2,3-d]pyrimidin-4-amine
• CAS: 1235310-91-4
• 化学式: C₂₃H₁₉N₅O
• 分子量: 381.437
• InChiKey: ZESPBXOCDIADDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  79.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-5,6-二苯基呋喃并[2,3-D]嘧啶 、 组胺 以 正丁醇 为溶剂， 反应 16.0h， 生成 (5,6-diphenylfuro[2,3-d]pyrimidin-4-yl)-[2-(1H-imidazol-4-yl)-ethyl]amine
  参考文献：
  名称：

  Fast-Forwarding Hit to Lead: Aurora and Epidermal Growth Factor Receptor Kinase Inhibitor Lead Identification

  摘要：

  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.

  DOI：

  10.1021/jm1000198

文献信息

• 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.