2-(4-hydroxyphenyl)-4H-pyrido[1,2-a]pyrimidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(4-hydroxyphenyl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 2-(4-hydroxyphenyl)pyrido[1,2-a]pyrimidin-4-one
• 化学式: C₁₄H₁₀N₂O₂
• 分子量: 238.246
• InChiKey: IPWAZFNQCNMGAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(4-methoxyphenyl)-4H-pyrido[1,2-a]pyrimidin-4-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以74%的产率得到2-(4-hydroxyphenyl)-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  吡啶并[1,2-a]嘧啶-4-酮衍生物作为一类新型的选择性醛糖还原酶抑制剂，具有抗氧化活性。

  摘要：

  测试了在2位带有酚或邻苯二酚部分的2-苯基-吡啶并[1,2-a]嘧啶-4-酮衍生物作为醛糖还原酶（ALR2）抑制剂的活性，其活性水平在微摩尔/亚微摩尔范围内。在位置6或9引入羟基可增强抑制能力（比较18、19、28和29与13和14）。2-侧链加长至苄基决定了活性的普遍降低。苯酚或邻苯二酚羟基的缺乏或甲基化会导致无活性（10-12、21、22、25-27）或几乎没有活性（15、17、20）的化合物，因此表明苯酚或邻苯二酚的羟基参与了酶药效学识别。此外，所有的嘧啶并嘧啶酮均显示出显着的抗氧化性能，儿茶酚衍生物显示出最佳的活性。

  DOI：

  10.1021/jm070398a

文献信息

• Scaffold-hopping of bioactive flavonoids: Discovery of aryl-pyridopyrimidinones as potent anticancer agents that inhibit catalytic role of topoisomerase IIα
  作者：Garima Priyadarshani、Suyog Amrutkar、Anmada Nayak、Uttam C. Banerjee、Chanakya N. Kundu、Sankar K. Guchhait

  DOI：10.1016/j.ejmech.2016.06.024

  日期：2016.10

  A strategy of scaffold-hopping of bioactive natural products, flavones and isofl avones, leading to target-based discovery of potent anticancer agents has been reported for the first time. Scaffold-hopped flavones, 2-aryl-4H-pyrido[1,2-a]pyrimidin-4-ones and the scaffold-hopped isofiavones, 3-aryl-pyrido[1,2-a]pyrimidin-4-ones were synthesized via Pd-catalyzed activation-arylation methods. Most of the compounds were found to exhibit pronounced human topoisomerase II alpha (hTopoll alpha) inhibitory activities and several compounds were found to be more potent than etoposide (a hTopoll alpha-inhibiting anticancer drug). These classes of compounds were found to be hTopoll alpha-selective catalytic inhibitors while not interfering with topoisomerase I and interacted with DNA plausibly in groove domain. Cytotoxicities against various cancer cells, low toxicity in normal cells, and apoptotic effects were observed. Interestingly, compared to parent flavones/isoflavones, their scaffold-hopped analogs bearing alike functionalities showed significant/enhanced hTopoII alpha-inhibitory and cytotoxic properties, indicating the importance of a natural product-based scaffold-hopping strategy in the drug discovery. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Pyrido[1,2-<i>a</i>]pyrimidin-4-one Derivatives as a Novel Class of Selective Aldose Reductase Inhibitors Exhibiting Antioxidant Activity
  作者：Concettina La Motta、Stefania Sartini、Laura Mugnaini、Francesca Simorini、Sabrina Taliani、Silvia Salerno、Anna Maria Marini、Federico Da Settimo、Antonio Lavecchia、Ettore Novellino、Miriam Cantore、Paola Failli、Mario Ciuffi

  DOI：10.1021/jm070398a

  日期：2007.10.1

  2-Phenyl-pyrido[1,2-a]pyrimidin-4-one derivatives bearing a phenol or a catechol moiety in position 2 were tested as aldose reductase (ALR2) inhibitors and exhibited activity levels in the micromolar/submicromolar range. Introduction of a hydroxy group in position 6 or 9 gave an enhancement of the inhibitory potency (compare 18, 19, 28, and 29 vs 13 and 14). Lengthening of the 2-side chain to benzyl

  测试了在2位带有酚或邻苯二酚部分的2-苯基-吡啶并[1,2-a]嘧啶-4-酮衍生物作为醛糖还原酶（ALR2）抑制剂的活性，其活性水平在微摩尔/亚微摩尔范围内。在位置6或9引入羟基可增强抑制能力（比较18、19、28和29与13和14）。2-侧链加长至苄基决定了活性的普遍降低。苯酚或邻苯二酚羟基的缺乏或甲基化会导致无活性（10-12、21、22、25-27）或几乎没有活性（15、17、20）的化合物，因此表明苯酚或邻苯二酚的羟基参与了酶药效学识别。此外，所有的嘧啶并嘧啶酮均显示出显着的抗氧化性能，儿茶酚衍生物显示出最佳的活性。