2-amino-8-methoxy-5H-benzo[3',2':5,6]thiopyrano[4,3-d]pyrimidine | 1041183-01-0

• 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-amino-8-methoxy-5H-benzo[3',2':5,6]thiopyrano[4,3-d]pyrimidine
• 英文别名: 2-amino-8-methoxy-5H-benzothiopyrano[4,3-d]pyrimidine；8-methoxy-5H-thiochromeno[4,3-d]pyrimidin-2-amine
• CAS: 1041183-01-0
• 化学式: C₁₂H₁₁N₃OS
• 分子量: 245.305
• InChiKey: WAFPZDREZUDFNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-8-methoxy-5H-benzo[3',2':5,6]thiopyrano[4,3-d]pyrimidine 、 对氯碘苯 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以35%的产率得到8-methoxy-2-(p-chloroanilino)-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
• 作为产物：
  描述：

  7-甲氧基硫代苯并二氢吡喃-4-酮 在 sodium ethanolate 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 2-amino-8-methoxy-5H-benzo[3',2':5,6]thiopyrano[4,3-d]pyrimidine
  参考文献：
  名称：

  在2-苯基氨基取代的苯并硫吡喃并[4,3- d ]嘧啶作为激酶抑制剂的结构-活性关系中的新见解

  摘要：

  通过阻断血管内皮生长因子受体（VEGFR）信号传导通路抑制血管生成已成为抗癌治疗中的一项既定方法。到目前为止，许多单克隆抗体和具有ATP竞争能力的小分子抑制剂已在临床上得到验证和认可。在这项研究中，通过合成和生物学评估具有不同取代方式的新化合物1-21，进一步细化了2-苯基氨基取代的苯并硫吡喃并[4,3- d ]嘧啶类激酶抑制剂之间的结构-活性关系（SAR）在苯基侧基上，在8位与H，OCH 3或Cl结合。大多数化合物显示出有前途的人激酶插入结构域受体（KDR）抑制谱，IC 50值在亚微摩尔/低微摩尔范围内，并且有望对人脐静脉内皮细胞（HUVEC）以及一组三种人肿瘤细胞系具有抗增殖活性。针对最有前途的化合物16评估了针对一组六个人类激酶的血管激酶选择性谱。最后，计算研究允许在分子水平上阐明具有KDR的化合物建立的相互作用模式，突出了关键的稳定阳离子π相互作用，从而为进一步设计新型抑制剂提供了基础。

  DOI：

  10.1016/j.ejmech.2018.03.013

文献信息

• Synthesis and<i>in vitro</i>antiproliferative activity of new substituted benzo[3′,2′:5,6]thiopyrano[4,3-<i>d</i>]pyrimidines
  作者：Anna Maria Marini、Federico Da Settimo、Silvia Salerno、Concettina La Motta、Francesca Simorini、Sabrina Taliani、Daniele Bertini、Ornella Gia、Lisa Dalla Via

  DOI：10.1002/jhet.5570450318

  日期：2008.5

  The synthesis of new planar benzo[3′,2′:5,6]thiopyrano[4,3-d]pyrimidine derivatives, carrying different side groups in the 2 position, is described. The novel substituted pyrimidines were obtained by reaction of the key intermediate 3-dimethylamino methylen-7-methoxy-2,3-dihydrobenzo[3′,2′:5,6]thiopyran-4(4H)-one, characterized by a reactive group adjacent to the CO function, with the suitable binucleophile

  描述了新的平面苯并[3'，2'：5,6]硫代吡喃并[4,3- d ]嘧啶衍生物的合成，该衍生物在2位上带有不同的侧基。通过关键中间体3-二甲基氨基亚甲基-7-甲氧基-2,3-二氢苯并[3'，2'：5,6]硫吡喃-4（4 H）-1的反应获得新型取代的嘧啶。在碱性介质中具有合适的双亲核am，与CO官能团相邻的反应性基团。通过体外评估所有新化合物的抗增殖能力在两种人类肿瘤细胞系（HL-60和HeLa）上进行检测，发现2-苯基取代的衍生物具有抑制细胞在HL-60上生长的能力。线性流二色性测量表明不能与DNA形成分子复合物。
• 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.
• New insights in the structure-activity relationships of 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidines as kinase inhibitors
  作者：Silvia Salerno、Aída Nelly García-Argáez、Elisabetta Barresi、Sabrina Taliani、Francesca Simorini、Concettina La Motta、Giorgio Amendola、Stefano Tomassi、Sandro Cosconati、Ettore Novellino、Federico Da Settimo、Anna Maria Marini、Lisa Dalla Via

  DOI：10.1016/j.ejmech.2018.03.013

  日期：2018.4

  and ATP-competitive small molecule inhibitors have been clinically validated and approved. In this study, structure-activity relationships (SAR) within the 2-phenylamino-substituted benzothiopyrano[4,3-d]pyrimidine class of kinase inhibitors were further refined by the synthesis and biological evaluation of new compounds 1–21 featuring different substitution patterns on the pendant phenyl moiety, combined

  通过阻断血管内皮生长因子受体（VEGFR）信号传导通路抑制血管生成已成为抗癌治疗中的一项既定方法。到目前为止，许多单克隆抗体和具有ATP竞争能力的小分子抑制剂已在临床上得到验证和认可。在这项研究中，通过合成和生物学评估具有不同取代方式的新化合物1-21，进一步细化了2-苯基氨基取代的苯并硫吡喃并[4,3- d ]嘧啶类激酶抑制剂之间的结构-活性关系（SAR）在苯基侧基上，在8位与H，OCH 3或Cl结合。大多数化合物显示出有前途的人激酶插入结构域受体（KDR）抑制谱，IC 50值在亚微摩尔/低微摩尔范围内，并且有望对人脐静脉内皮细胞（HUVEC）以及一组三种人肿瘤细胞系具有抗增殖活性。针对最有前途的化合物16评估了针对一组六个人类激酶的血管激酶选择性谱。最后，计算研究允许在分子水平上阐明具有KDR的化合物建立的相互作用模式，突出了关键的稳定阳离子π相互作用，从而为进一步设计新型抑制剂提供了基础。