2-amino-5H-pyrido[3',2':5,6]thiopyrano[4,3-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-amino-5H-pyrido[3',2':5,6]thiopyrano[4,3-d]pyrimidine
• 英文别名: 9-Thia-3,5,11-triazatricyclo[8.4.0.02,7]tetradeca-1(10),2,4,6,11,13-hexaen-4-amine
• 化学式: C₁₀H₈N₄S
• 分子量: 216.266
• InChiKey: BKHQODNQFPFSIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  90
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-5H-pyrido[3',2':5,6]thiopyrano[4,3-d]pyrimidine 、 4-碘藜芦醚 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2-(3,4-dimethoxyanilino)-5H-pyrido[3',2':5,6]thiopyrano[4,3-d]pyrimidine
  参考文献：
  名称：

  Discovery of Pyrido[3′,2′:5,6]thiopyrano[4,3-d]pyrimidine-Based Antiproliferative Multikinase Inhibitors

  摘要：

  Protein kinases dysregulation is extremely common in cancer cells, and the development of new agents able to simultaneously target multiple kinase pathways involved in angiogenesis and tumor growth may offer several advantages in the treatment of cancer. Herein we report the discovery of new pyridothiopyranopyrimidine derivatives (2-4) showing high potencies in VEGFR-2 KDR inhibition as well as antiproliferative effect on a panel of human tumor cell lines. Investigation on the selectivity profile of the representative 2-anilino-substituted compounds 3b, 3i, and 3j revealed a multiplicity of kinase targets that should account for the potent antiproliferative effect produced by these pyridothiopyranopyrimidine derivatives.

  DOI：

  10.1021/acsmedchemlett.8b00499
• 作为产物：
  描述：

  2,3-dihydro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-one 、 盐酸胍 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以60%的产率得到2-amino-5H-pyrido[3',2':5,6]thiopyrano[4,3-d]pyrimidine
  参考文献：
  名称：

  Mitochondrial permeability transition induced by novel pyridothiopyranopyrimidine derivatives: Potential new antimitochondrial antitumour agents

  摘要：

  New pyridothiopyranopyrimidine derivatives (PTP1 and PTP2) were synthesised. Evaluation of the antiproliferative activity showed a significant capacity of the two compounds to inhibit cell growth. Investigation of the mechanism of action reveals that PTP1 interferes with the mitochondrial functions by inducing both swelling of the mitochondrial. matrix and collapse of the electrical potential. These phenomena are fully prevented by typical inhibitors of the mitochondrial permeability transition, and are accompanied by the release of cytochromecin the cytosol. The estimation of the redox state of thiol groups and glutathione suggests that the induction of permeability transition mediated by PTP1 is the result of an oxidative stress. The ability of cyclosporin A to prevent the antiproliferative effect of PTP1 indicates the induction of mitochondrial permeability transition as the molecular event responsible for the inhibition of cell growth. PTP1 also induces DNA fragmentation in intact cells.As regards PTP2, the presence of the p-toluensulphonamido group makes the lead chromophore unable to induce any effect on mitochondria. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2006.07.033

文献信息

• Mitochondrial permeability transition induced by novel pyridothiopyranopyrimidine derivatives: Potential new antimitochondrial antitumour agents
  作者：Lisa Dalla Via、Anna Maria Marini、Silvia Salerno、Antonio Toninello

  DOI：10.1016/j.bcp.2006.07.033

  日期：2006.12

  New pyridothiopyranopyrimidine derivatives (PTP1 and PTP2) were synthesised. Evaluation of the antiproliferative activity showed a significant capacity of the two compounds to inhibit cell growth. Investigation of the mechanism of action reveals that PTP1 interferes with the mitochondrial functions by inducing both swelling of the mitochondrial. matrix and collapse of the electrical potential. These phenomena are fully prevented by typical inhibitors of the mitochondrial permeability transition, and are accompanied by the release of cytochromecin the cytosol. The estimation of the redox state of thiol groups and glutathione suggests that the induction of permeability transition mediated by PTP1 is the result of an oxidative stress. The ability of cyclosporin A to prevent the antiproliferative effect of PTP1 indicates the induction of mitochondrial permeability transition as the molecular event responsible for the inhibition of cell growth. PTP1 also induces DNA fragmentation in intact cells.As regards PTP2, the presence of the p-toluensulphonamido group makes the lead chromophore unable to induce any effect on mitochondria. (c) 2006 Elsevier Inc. All rights reserved.
• Discovery of Pyrido[3′,2′:5,6]thiopyrano[4,3-<i>d</i>]pyrimidine-Based Antiproliferative Multikinase Inhibitors
  作者：Silvia Salerno、Elisabetta Barresi、Aída Nelly García-Argáez、Sabrina Taliani、Francesca Simorini、Giorgio Amendola、Stefano Tomassi、Sandro Cosconati、Ettore Novellino、Federico Da Settimo、Anna Maria Marini、Lisa Dalla Via

  DOI：10.1021/acsmedchemlett.8b00499

  日期：2019.4.11

  Protein kinases dysregulation is extremely common in cancer cells, and the development of new agents able to simultaneously target multiple kinase pathways involved in angiogenesis and tumor growth may offer several advantages in the treatment of cancer. Herein we report the discovery of new pyridothiopyranopyrimidine derivatives (2-4) showing high potencies in VEGFR-2 KDR inhibition as well as antiproliferative effect on a panel of human tumor cell lines. Investigation on the selectivity profile of the representative 2-anilino-substituted compounds 3b, 3i, and 3j revealed a multiplicity of kinase targets that should account for the potent antiproliferative effect produced by these pyridothiopyranopyrimidine derivatives.