7-(4-bromophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione | 108903-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 7-(4-bromophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione
• 英文别名: 7-(4-bromophenyl)-1H-pyrido[2,3-d]pyrimidine-2,4-dione
• CAS: 108903-06-6
• 化学式: C₁₃H₈BrN₃O₂
• 分子量: 318.129
• InChiKey: FNCDSFCKIPDNFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 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：
  71.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴苯乙酮 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 7-(4-bromophenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  First‐in‐class pyrido[2,3‐ d ]pyrimidine‐2,4(1 H ,3 H )‐diones against leishmaniasis and tuberculosis: Rationale, in vitro, ex vivo studies and mechanistic insights

  摘要：

  AbstractPyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones were synthesized, for the first time, from indole chalcones and 6‐aminouracil, and their ability to inhibit leishmaniasis and tuberculosis (Tb) infections was evaluated. The in vitro antileishmanial activity against promastigotes of Leishmania donovani revealed exceptional activities of compounds 3, 12 and 13, with IC50 values ranging from 10.23 ± 1.50 to 15.58 ± 1.67 µg/ml, which is better than the IC50 value of the standard drug pentostam of 500 μg/ml. The selectivity of the compounds towards Leishmania parasites was evaluated via ex vivo studies in Swiss albino mice. The efficiency of these compounds against Tb infection was then evaluated using the in vitro anti‐Tb microplate Alamar Blue assay. Five compounds, 3, 7, 8, 9 and 12, showed MIC100 values against the Mycobacterium tuberculosis H37Rv strain at 25 µg/ml, and compound 20 yielded an MIC100 value of 50 µg/ml. Molecular modelling of these compounds highlighted interactions with binding sites of dihydrofolate reductase, pteridine reductase and thymidylate kinase, thus establishing the rationale of their pharmacological activity against both pathogens, which is consistent with the in vitro results. From the above results, it is clear that compounds 3 and 12 are promising lead candidates for Leishmania and Mycobacterium infections and may be promising for coinfections.

  DOI：

  10.1002/ardp.202100440

文献信息

• Improved synthesis of substituted pyrido[2,3-d]pyrimidinediones
  作者：Gwydion H. Churchill、Steven A. Raw、Lyn Powell

  DOI：10.1016/j.tetlet.2011.05.021

  日期：2011.7

  An improved methodology for the synthesis of substituted pyrido[2,3-d]pyrimidinediones from 6-aminouracils and the corresponding enaminone has been developed which provides high yields via an operationally simple process. The method has been extended to encompass a range of electron-rich enaminones, a substrate class that does not perform well under the standard conditions.

  已经开发了一种由6-氨基尿嘧啶和相应的烯胺酮合成取代的吡啶并[2,3- d ]嘧啶二酮的改进方法，该方法可通过操作简单的方法提供高收率。该方法已扩展到涵盖一系列富电子烯键酮，这是在标准条件下不能很好发挥作用的底物类型。
• First‐in‐class pyrido[2,3‐ <i>d</i> ]pyrimidine‐2,4(1 <i>H</i> ,3 <i>H</i> )‐diones against leishmaniasis and tuberculosis: Rationale, in vitro, ex vivo studies and mechanistic insights
  作者：Deepthi Ramesh、Deblina Sarkar、Annu Joji、Monica Singh、Amaresh K. Mohanty、Balaji G. Vijayakumar、Mitali Chatterjee、Dharmarajan Sriram、Suresh K. Muthuvel、Tharanikkarasu Kannan

  DOI：10.1002/ardp.202100440

  日期：2022.4

  AbstractPyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones were synthesized, for the first time, from indole chalcones and 6‐aminouracil, and their ability to inhibit leishmaniasis and tuberculosis (Tb) infections was evaluated. The in vitro antileishmanial activity against promastigotes of Leishmania donovani revealed exceptional activities of compounds 3, 12 and 13, with IC50 values ranging from 10.23 ± 1.50 to 15.58 ± 1.67 µg/ml, which is better than the IC50 value of the standard drug pentostam of 500 μg/ml. The selectivity of the compounds towards Leishmania parasites was evaluated via ex vivo studies in Swiss albino mice. The efficiency of these compounds against Tb infection was then evaluated using the in vitro anti‐Tb microplate Alamar Blue assay. Five compounds, 3, 7, 8, 9 and 12, showed MIC100 values against the Mycobacterium tuberculosis H37Rv strain at 25 µg/ml, and compound 20 yielded an MIC100 value of 50 µg/ml. Molecular modelling of these compounds highlighted interactions with binding sites of dihydrofolate reductase, pteridine reductase and thymidylate kinase, thus establishing the rationale of their pharmacological activity against both pathogens, which is consistent with the in vitro results. From the above results, it is clear that compounds 3 and 12 are promising lead candidates for Leishmania and Mycobacterium infections and may be promising for coinfections.