8-chloro-2-(p-methoxyphenyl)-5H-benzothiopyrane[4,3-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻喃类
• 英文名称: 8-chloro-2-(p-methoxyphenyl)-5H-benzothiopyrane[4,3-d]pyrimidine
• 英文别名: 8-chloro-2-(4-methoxyphenyl)-5H-thiochromeno[4,3-d]pyrimidine
• 化学式: C₁₈H₁₃ClN₂OS
• 分子量: 340.833
• InChiKey: OZFJDRNXWBYJFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-chloro-3-dimethylaminomethylen-2,3-dihydro-benzo[3',2':5,6]thiopyran-4(4H)-one 、 4-甲氧基苄脒盐酸盐 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 6.25h， 以13%的产率得到8-chloro-2-(p-methoxyphenyl)-5H-benzothiopyrane[4,3-d]pyrimidine
  参考文献：
  名称：

  Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d]pyrimidines as kinase inhibitors targeting vascular endothelial growth factor receptor 2

  摘要：

  Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of Angiogenesis, a central process implicated in tumour growth and metastatic dissemination. This led to the design and development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive VEGFR-inhibitors. In this study, we describe the synthesis and the biological evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a-i and 3a-i. The ability of the compounds to target the VEGF pathway was determined in vitro exploiting the compounds' anti-proliferative efficacy against HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on recombinant human kinase insert domain receptor (KDR), by cell-based phospho-VEGFR-2 inhibition assays, and by ex vivo rat aortic ring tests. The selectivity profile of the best performing derivatives belonging to series 2 was further explored combining modeling studies and additional assays in a panel of human cell lines and other kinases. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.08.027

文献信息

• Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d]pyrimidines as kinase inhibitors targeting vascular endothelial growth factor receptor 2
  作者：Silvia Salerno、Anna Maria Marini、Giacomo Fornaciari、Francesca Simorini、Concettina La Motta、Sabrina Taliani、Stefania Sartini、Federico Da Settimo、Aída Nelly García-Argáez、Ornella Gia、Sandro Cosconati、Ettore Novellino、Pilar D'Ocon、Anna Fioravanti、Paola Orlandi、Guido Bocci、Lisa Dalla Via

  DOI：10.1016/j.ejmech.2015.08.027

  日期：2015.10

  Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of Angiogenesis, a central process implicated in tumour growth and metastatic dissemination. This led to the design and development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive VEGFR-inhibitors. In this study, we describe the synthesis and the biological evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a-i and 3a-i. The ability of the compounds to target the VEGF pathway was determined in vitro exploiting the compounds' anti-proliferative efficacy against HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on recombinant human kinase insert domain receptor (KDR), by cell-based phospho-VEGFR-2 inhibition assays, and by ex vivo rat aortic ring tests. The selectivity profile of the best performing derivatives belonging to series 2 was further explored combining modeling studies and additional assays in a panel of human cell lines and other kinases. (C) 2015 Published by Elsevier Masson SAS.