2-amino-5H-benzothiopyrano[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: 2-amino-5H-benzothiopyrano[4,3-d]pyrimidine
• 英文别名: 5H-thiochromeno[4,3-d]pyrimidin-2-amine
• 化学式: C₁₁H₉N₃S
• 分子量: 215.279
• InChiKey: JJQILBQGDPEKNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  对氯碘苯 、 2-amino-5H-benzothiopyrano[4,3-d]pyrimidine 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23%的产率得到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：

  3-苯硫基丙酸 在 硫酸 作用下， 反应 19.0h， 生成 2-amino-5H-benzothiopyrano[4,3-d]pyrimidine
  参考文献：
  名称：

  新型5H-硫代色素[4,3-d]嘧啶的合成及其抗宫颈癌活性

  摘要：

  通过不同的光谱技术，如1H NMR，13C NMR，质量和元素分析，合成，纯化和表征了一系列新颖的5H-硫代色素[4,3-d]嘧啶衍生物。评价了这些新化合物对人宫颈细胞系HeLa的抗宫颈癌活性。发现它们是有效的抗宫颈癌药物，相对于阳性对照药物阿霉素，GI50值小于10μg/ mL。

  DOI：

  10.2174/1570178616666190705152116

文献信息

• Cu/<i>N</i>,<i>N</i>′-Dibenzyloxalamide-Catalyzed <i>N</i>-Arylation of Heteroanilines
  作者：Zhixiang Chen、Dawei Ma

  DOI：10.1021/acs.orglett.9b02509

  日期：2019.9.6

  N,N'-Dibenzyloxalamide (DBO) was identified as a powerful ligand for promoting Cu-catalyzed coupling of heteroanilines with (hetero)aryl halides. For (hetero)aryl chlorides, the coupling reaction occurred at 130 °C with 5 mol % CuBr and 10 mol % DBO. For (hetero)aryl bromides/iodides, coupling reaction took place at 80-100 °C with 1 mol % CuI and 2 mol % DBO. A variety of heteroanilines worked well

  N，N'-二苄基草酰胺（DBO）被确定为一种强大的配体，用于促进Cu催化杂苯胺与（杂）芳基卤化物的偶联。对于（杂）芳基氯，偶联反应在130℃下与5mol％的CuBr和10mol％的DBO发生。对于（杂）芳基溴化物/碘化物，偶合反应在80-100°C下与1 mol％的CuI和2 mol％的DBO进行。各种杂苯胺效果很好，以高到极高的收率提供了芳基化产物。
• 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。
• New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: synthesis and pharmacological screening
  作者：Olga Bruno、Silvia Schenone、Angelo Ranise、Francesco Bondavalli、Elisabetta Barocelli、Vigilio Ballabeni、Milena Chiavarini、Simona Bertoni、Massimiliano Tognolini、Mariannina Impicciatore

  DOI：10.1016/s0968-0896(00)00272-8

  日期：2001.3

  The preparation and the pharmacological screening of novel anti-aggregatory/antiphlogistic polycyclic pyrimidine derivatives are described. The compounds were developed starting from bioactive 2-aminobenzopyranopyrimidine derivatives in order to assess the importance of the benzopyrano[4,3-d]pyrimidine structure and the role of an amino basic moiety in position 2. Antiplatelet activity was assessed in vitro against ADP and arachidonic acid-induced aggregation in guinea-pig plasma. Anti-inflammatory analgesic/antipyretic activities were studied in rat paw oedema, mouse writhing test and E coli-induced rat fever. Ulcerogenic and gastroprotective effects were also investigated in vivo on rat gastric mucosa. Among the tested compounds, the 5-substituted benzopyranopyrimidine derivatives 3d and 4d proved to be the most active antiplatelet agents as potent as acetylsalicylic acid against arachidonic acid-stimulated aggregation. Furthermore the 2-methylthio derivative 4d was endowed with greater efficacy against ADP aggregation suggesting that additional non-TXA(2) dependent mechanisms are involved in its biological activity. Orally administered at 100 mg kg(-1) in rats this latter compound displayed antiphlogistic acitivity comparable to indomethacin (10 mg kg(-1)) coupled with an unusual gastroprotective effect on ethanol-induced ulcers. In conclusion, these findings indicate that the 5-pyrrolidino-2-methylthiobenzopyrano[4d] fulfils the chemical requirements to exhibit antiplatelet activity associated with gastroprotective effect. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 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.
• Synthesis and Anti Cervical Cancer Activity of Novel 5H-Thiochromeno [4,3-d]pyrimidines
  作者：Dhananjay Pandya、Yogesh Naliapara

  DOI：10.2174/1570178616666190705152116

  日期：2020.3.25

  A series of novel 5H-Thiochromeno[4,3-d]pyrimidine derivatives were synthesized, purified and characterized by different spectroscopy techniques such as 1H NMR, 13C NMR, Mass and Elemental Analysis. The new compounds were evaluated for their anti-cervical cancer activity on Human Cervical Cell Line HeLa. They were found to be potent anti-cervical cancer agents with GI50 values less than 10 μg/mL with

  通过不同的光谱技术，如1H NMR，13C NMR，质量和元素分析，合成，纯化和表征了一系列新颖的5H-硫代色素[4,3-d]嘧啶衍生物。评价了这些新化合物对人宫颈细胞系HeLa的抗宫颈癌活性。发现它们是有效的抗宫颈癌药物，相对于阳性对照药物阿霉素，GI50值小于10μg/ mL。