N-(2-methoxybenzyl)benzo[4,5]thieno[3,2-d]pyrimidin-4-amine | 1414524-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: N-(2-methoxybenzyl)benzo[4,5]thieno[3,2-d]pyrimidin-4-amine
• 英文别名: N-[(2-methoxyphenyl)methyl]-[1]benzothiolo[3,2-d]pyrimidin-4-amine
• CAS: 1414524-09-6
• 化学式: C₁₈H₁₅N₃OS
• 分子量: 321.403
• InChiKey: PZEKZXQPSRLEGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基苯并[b]噻吩-2-羧酸甲酯 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.75h， 生成 N-(2-methoxybenzyl)benzo[4,5]thieno[3,2-d]pyrimidin-4-amine
  参考文献：
  名称：

  Synthesis and evaluation of apoptosis induction of thienopyrimidine compounds on KRAS and BRAF mutated colorectal cancer cell lines

  摘要：

  Monoclonal antibodies (MoAb) and tyrosine kinase inhibitors (TKI) targeting the EGFR (Epidermal Growth Factor Receptor) pathways are currently used in colorectal cancer treatment. Despite the improvement of median overall survival, resistance is observed notably due to KRAS and BRAF gene mutations. We synthesized four series of thienopyrimidines whose scaffold is structurally close to TKI used in clinical practice. We evaluated apoptosis induced by these compounds using flow cytometry on KRAS and BRAF mutated cell lines. Our results confirm that the mutated cell lines (HCT116 and HT29) are more resistant to apoptosis than the non-mutated cell line (Hela). Interestingly, among the 13 compounds tested, three of them (5b, 6b and 6d) and gefitinib exhibited a noteworthy pro-apoptotic effect, especially on mutated cell lines with an IC50 value between 70 and 110 mu M. These three compounds seem particularly attractive for the development of novel treatments for colorectal cancer patients harboring EGFR pathway mutations. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.034

文献信息

• Synthesis and evaluation of apoptosis induction of thienopyrimidine compounds on KRAS and BRAF mutated colorectal cancer cell lines
  作者：Stéphane Pédeboscq、Denis Gravier、Françoise Casadebaig、Geneviève Hou、Arnaud Gissot、Christophe Rey、François Ichas、Francesca De Giorgi、Lydia Lartigue、Jean-Paul Pometan

  DOI：10.1016/j.bmc.2012.09.034

  日期：2012.11

  Monoclonal antibodies (MoAb) and tyrosine kinase inhibitors (TKI) targeting the EGFR (Epidermal Growth Factor Receptor) pathways are currently used in colorectal cancer treatment. Despite the improvement of median overall survival, resistance is observed notably due to KRAS and BRAF gene mutations. We synthesized four series of thienopyrimidines whose scaffold is structurally close to TKI used in clinical practice. We evaluated apoptosis induced by these compounds using flow cytometry on KRAS and BRAF mutated cell lines. Our results confirm that the mutated cell lines (HCT116 and HT29) are more resistant to apoptosis than the non-mutated cell line (Hela). Interestingly, among the 13 compounds tested, three of them (5b, 6b and 6d) and gefitinib exhibited a noteworthy pro-apoptotic effect, especially on mutated cell lines with an IC50 value between 70 and 110 mu M. These three compounds seem particularly attractive for the development of novel treatments for colorectal cancer patients harboring EGFR pathway mutations. (C) 2012 Elsevier Ltd. All rights reserved.