(E)-1-(4-[(1S)-2-hydroxy-1-phenylethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7-yl)-3-phenyl-2-propen-1-one | 1226548-22-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-1-(4-[(1S)-2-hydroxy-1-phenylethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7-yl)-3-phenyl-2-propen-1-one
• 英文别名: (E)-1-[3-[[(1S)-2-hydroxy-1-phenylethyl]amino]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6-tetraen-11-yl]-3-phenylprop-2-en-1-one
• CAS: 1226548-22-6
• 化学式: C₂₆H₂₄N₄O₂S
• 分子量: 456.568
• InChiKey: BZNVJBJWWCQQET-RJRNSMGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  肉桂酸 、 (S)-2-Phenyl-2-((5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-yl)amino)ethan-1-ol 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (E)-1-(4-[(1S)-2-hydroxy-1-phenylethyl]amino-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7-yl)-3-phenyl-2-propen-1-one
  参考文献：
  名称：

  Design and Synthesis of Tetrahydropyridothieno[2,3-d]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency

  摘要：

  HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.

  DOI：

  10.1021/jm100607r

文献信息

• Fused Bicyclic and Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors
  申请人：Hsieh Hsing-Pang

  公开号：US20100120805A1

  公开（公告）日：2010-05-13

  Fused bicyclic or tricyclic compounds of formula (I): wherein A, B, C, X, Y, m, and n are defined herein. Also disclosed are a method for inhibiting EGFR kinase activity and a method for treating cancer with these compounds.

  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。
• 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.
• Design and Synthesis of Tetrahydropyridothieno[2,3-<i>d</i>]pyrimidine Scaffold Based Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors: The Role of Side Chain Chirality and Michael Acceptor Group for Maximal Potency
  作者：Chia-Hsien Wu、Mohane Selvaraj Coumar、Chang-Ying Chu、Wen-Hsing Lin、Yi-Rong Chen、Chiung-Tong Chen、Hui-Yi Shiao、Shaik Rafi、Sing-Yi Wang、Hui Hsu、Chun-Hwa Chen、Chun-Yu Chang、Teng-Yuan Chang、Tzu-Wen Lien、Ming-Yu Fang、Kai-Chia Yeh、Ching-Ping Chen、Teng-Kuang Yeh、Su-Huei Hsieh、John T.-A. Hsu、Chun-Chen Liao、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1021/jm100607r

  日期：2010.10.28

  HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.