2,3-dihydro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-one | 640265-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 2,3-dihydro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-one
• 英文别名: 3-(dimethylaminomethylidene)thiopyrano[2,3-b]pyridin-4-one
• CAS: 640265-21-0
• 化学式: C₁₁H₁₂N₂OS
• 分子量: 220.295
• InChiKey: VUAZWIKBFJJWIS-UHFFFAOYSA-N

物化性质

• 熔点：
  100-101 °C(Solv: ligroine (8032-32-4); toluene (108-88-3))
• 沸点：
  374.2±42.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.82
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  33.2
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  盐酸乙脒 、 2,3-dihydro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-one 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 6.25h， 以58%的产率得到4-Methyl-9-thia-3,5,11-triazatricyclo[8.4.0.02,7]tetradeca-1(10),2,4,6,11,13-hexaene
  参考文献：
  名称：

  新型1,4-二氢吡啶并[3'，2'：5,6]硫代吡喃并[4,3- c ]-吡唑和5 H-吡啶并[3'，2'：5,6]硫代吡喃并[4,3 - d ]嘧啶作为潜在的抗增殖剂

  摘要：

  据报道，以具有取代的芳基的吡啶硫代吡喃并吡唑或吡啶硫吡喃并嘧啶核的存在为特征的新的平面衍生物的合成。通过2,3-二氢-3-羟基亚甲基硫代吡喃并[ 2,3- b ]吡啶的缩合反应，得到了新型的1,4-二氢吡啶并[3'，2'：5,6]硫代吡喃并[4,3- c ]吡唑衍生物。-4（4 H）-ones与适当的肼。由中间体2,3-二氢-dro-3-二甲基氨基亚甲基硫代吡喃并[ 2,3- b ]制备2-取代的吡啶并[3'，2'：5,6]硫代吡喃并[4,3- d ]嘧啶。吡啶-4（4 H）-通过与适当的双亲核am反应而得到的。通过体外试验对人肿瘤细胞系（HL-60和HeLa）测试了某些新产品的抗增殖活性，但在所进行的测试中均未显示任何明显的作用。因此，线性流二色性测量表明它们不能与DNA形成分子复合物。

  DOI：

  10.1002/jhet.5570400506
• 作为产物：
  描述：

  N,N-二甲基甲酰胺二甲基缩醛 、 2,3-二氢吡喃并[2,3-b]吡啶-4(4H)-酮 以 甲苯 为溶剂， 反应 16.0h， 以73.5%的产率得到2,3-dihydro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-one
  参考文献：
  名称：

  新型1,4-二氢吡啶并[3'，2'：5,6]硫代吡喃并[4,3- c ]-吡唑和5 H-吡啶并[3'，2'：5,6]硫代吡喃并[4,3 - d ]嘧啶作为潜在的抗增殖剂

  摘要：

  据报道，以具有取代的芳基的吡啶硫代吡喃并吡唑或吡啶硫吡喃并嘧啶核的存在为特征的新的平面衍生物的合成。通过2,3-二氢-3-羟基亚甲基硫代吡喃并[ 2,3- b ]吡啶的缩合反应，得到了新型的1,4-二氢吡啶并[3'，2'：5,6]硫代吡喃并[4,3- c ]吡唑衍生物。-4（4 H）-ones与适当的肼。由中间体2,3-二氢-dro-3-二甲基氨基亚甲基硫代吡喃并[ 2,3- b ]制备2-取代的吡啶并[3'，2'：5,6]硫代吡喃并[4,3- d ]嘧啶。吡啶-4（4 H）-通过与适当的双亲核am反应而得到的。通过体外试验对人肿瘤细胞系（HL-60和HeLa）测试了某些新产品的抗增殖活性，但在所进行的测试中均未显示任何明显的作用。因此，线性流二色性测量表明它们不能与DNA形成分子复合物。

  DOI：

  10.1002/jhet.5570400506

文献信息

• Sulfonamides incorporating heteropolycyclic scaffolds show potent inhibitory action against carbonic anhydrase isoforms I, II, IX and XII
  作者：Elisabetta Barresi、Silvia Salerno、Anna Maria Marini、Sabrina Taliani、Concettina La Motta、Francesca Simorini、Federico Da Settimo、Daniela Vullo、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2016.01.018

  日期：2016.2

  Three series of polycyclic compounds possessing either primary sulfonamide or carboxylic acid moieties as zinc-binding groups were investigated as inhibitors of four physiologically relevant CA isoforms, the cytosolic hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides reported here showed excellent inhibitory effects against isoforms hCA II, IX and XII, but no highly

  研究了具有伯磺酰胺或羧酸部分作为锌结合基团的三个系列多环化合物作为四种生理相关的CA同工型（胞质hCA I和II，以及跨膜hCA IX和XII）的抑制剂。此处报道的大多数新磺酰胺类药物对hCA II，IX和XII亚型均表现出优异的抑制作用，但没有高度的亚型选择性抑制谱。在另一方面，羧酸盐选择性抑制HCA IX（ķ我小号测距40.8和92.7纳米之间）而不抑制显著其它同种型。结合了多环系统的磺酰胺/羧酸盐，例如苯并硫代吡喃并嘧啶，吡啶并硫代吡喃并嘧啶或二氢苯并噻吩并吡喃并[4,3- c]吡唑可能被认为是探索具有各种药理应用的异构体选择性CAI设计的有趣候选物。
• 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.
• 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.