2-anilino-5H-benzothiopyrane[4,3-d]pyrimidine | 851023-78-4

• 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: 2-anilino-5H-benzothiopyrane[4,3-d]pyrimidine
• 英文别名: N-phenyl-5H-thiochromeno[4,3-d]pyrimidin-2-amine
• CAS: 851023-78-4
• 化学式: C₁₇H₁₃N₃S
• 分子量: 291.376
• InChiKey: AGZSNVJEBZAQKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(Dimethylaminomethylene)-4-thiochromanone 在 copper(l) iodide 、 盐酸胍 、 sodium ethanolate 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 30.0h， 生成 2-anilino-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

• COMPOSITIONS USEFUL AS INHIBITORS OF PROTEIN KINASES
  申请人：Jimenez Juan-Miguel

  公开号：US20100280026A1

  公开（公告）日：2010-11-04

  The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides processes for preparing the compounds, pharmaceutically acceptable compositions comprising the compounds, and methods of using the compounds and compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及作为蛋白激酶抑制剂有用的化合物。该发明还提供了制备这些化合物的方法，包括这些化合物的药学上可接受的组合物，以及使用这些化合物和组合物治疗各种疾病、状况或障碍的方法。
• US7700609B2
  申请人：——

  公开号：US7700609B2

  公开（公告）日：2010-04-20
• US8017619B2
  申请人：——

  公开号：US8017619B2

  公开（公告）日：2011-09-13
• US8288400B2
  申请人：——

  公开号：US8288400B2

  公开（公告）日：2012-10-16
• 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.