S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol | 1226548-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol
• 英文别名: (2s)-2-[(5,6-Diphenylfuro[2,3-D]pyrimidin-4-Yl)amino]-2-Phenylethanol
• CAS: 1226548-39-5
• 化学式: C₂₆H₂₁N₃O₂
• 分子量: 407.472
• InChiKey: CCGBAJCQZPJWCS-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 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：
  71.2
• 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 、 L-苯甘氨醇 以 正丁醇 为溶剂， 反应 16.0h， 以69%的产率得到S-2-(5,6-diphenylfuro[2,3-d]pyrimidin-4-ylamino)-2-phenylethanol
  参考文献：
  名称：

  Fused Bicyclic and Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors

  摘要：

  式(I)的融合双环或三环化合物： 其中A、B、C、X、Y、m和n在此处定义。还公开了一种抑制EGFR激酶活性的方法以及使用这些化合物治疗癌症的方法。

  公开号：

  US20100120805A1

文献信息

• Protein Kinase Inhibitor Design by Targeting the Asp-Phe-Gly (DFG) Motif: The Role of the DFG Motif in the Design of Epidermal Growth Factor Receptor Inhibitors
  作者：Yi-Hui Peng、Hui-Yi Shiao、Chih-Hsiang Tu、Pang-Min Liu、John Tsu-An Hsu、Prashanth Kumar Amancha、Jian-Sung Wu、Mohane Selvaraj Coumar、Chun-Hwa Chen、Sing-Yi Wang、Wen-Hsing Lin、Hsu-Yi Sun、Yu-Sheng Chao、Ping-Chiang Lyu、Hsing-Pang Hsieh、Su-Ying Wu

  DOI：10.1021/jm400072p

  日期：2013.5.23

  The Asp-Phe-Gly (DFG) motif plays an important role in the regulation of kinase activity. Structure-based drug design was performed to design compounds able to interact with the DFG motif; epidermal growth factor receptor (EGFR) was selected as an example. Structural insights obtained from the EGFR/2a complex suggested that an extension from the meta-position on the phenyl group (ring-5) would improve interactions with the DFG motif. Indeed, introduction of an N,N-dimethylamino tail resulted in 4b, which showed almost 50-fold improvement in inhibition compared to 2a. Structural studies confirmed this N,N-dimethylamino tail moved toward the DFG motif to form a salt bridge with the side chain of Asp831. That the interactions with the DFG motif greatly contribute to the potency of 4b is strongly evidenced by synthesizing and testing compounds 2a, 3g, and 4f: when the charge interactions are absent, the inhibitory activity decreased significantly.
• 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.
• US8507502B2
  申请人：——

  公开号：US8507502B2

  公开（公告）日：2013-08-13
• [EN] FUSED BICYCLIC AND TRICYCLIC PYRIMIDINE COMPOUNDS AS TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRIMIDINE BICYCLIQUES ET TRICYCLIQUES CONDENSÉS À TITRE D'INHIBITEURS DE TYROSINE KINASE
  申请人：NAT HEALTH RESEARCH INSTITUTES

  公开号：WO2010054285A2

  公开（公告）日：2010-05-14

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