2-(4-methylphenyl)pyrido[2,3-d]pyrimidin-4-one | 1613435-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-(4-methylphenyl)pyrido[2,3-d]pyrimidin-4-one
• 英文别名: 2-(4-methylphenyl)pyrido[2,3-d]pyrimidin-4(3H)-one；2-(4-methylphenyl)-3H-pyrido[2,3-d]pyrimidin-4-one
• CAS: 1613435-82-7
• 化学式: C₁₄H₁₁N₃O
• 分子量: 237.261
• InChiKey: IEAABOUDNZKBMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对甲苯腈 在 copper(l) iodide 、 palladium 10% on activated carbon 、 盐酸羟胺 、 甲酸铵 、 碳酸氢钠 、 caesium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 112.0h， 生成 2-(4-methylphenyl)pyrido[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  [EN] TANKYRASE INHIBITORS
  [FR] INHIBITEURS DE TANKYRASE

  摘要：

  本发明涉及一种具有式I的化合物，其中X为C(R6)或N，Y为C或N，环A、环B、R1和R2具有本文中定义的含义，前提是当环B为碳环时，X为C(R6)；或其药学上可接受的盐或溶剂。这些化合物是坦克酶-1和坦克酶-2抑制剂，并可用于治疗多种疾病，包括癌症。

  公开号：

  WO2014087165A1

文献信息

• An efficient transition-metal-free route to quinazolin-4(3<i>H</i>)-ones <i>via</i> 2-aminobenzamides and thiols
  作者：Yibo Dong、Jinli Zhang、Jinchen Yang、Congcong Yan、Yangjie Wu

  DOI：10.1039/d1nj03179a

  日期：——

  An efficient approach to quinazolin-4(3H)-ones was developed by a one-pot intermolecular annulation reaction of o-amino benzamides and thiols.

  通过一锅法，开发了一种高效的合成喹唑啉-4(3H)-酮的方法，该方法是通过对o-氨基苯甲酰胺和硫醇进行一种分子间环化反应实现的。
• A rapid construction of 4(3H)-quinazolinone and related ring under ultrasound irradiation: In silico/in vitro studies of compounds synthesized
  作者：Sidda Ramarao、Mohanreddy Pothireddy、Rapolu Venkateshwarlu、Krishna Murthy VR. Moturu、Vidavalur Siddaiah、Ravikumar Kapavarapu、Rambabu Dandela、Manojit Pal

  DOI：10.1016/j.molstruc.2022.134280

  日期：2023.2

  chemistry efforts have been devoted to establish convenient methods for the synthesis of quinazolinone derivatives. Due to our interest in this class of compounds as potential inhibitor chorismate mutase (MtbCM), a known target for the identification of anti-tubercular agents we report the rapid construction of 4(3H)-quinazolinone ring under ultrasound irradiation. The current sonochemical approach involved

  由于喹唑啉酮框架的重要性，特别是在药物和药物化学中的重要性，人们致力于建立合成喹唑啉酮衍生物的方便方法。由于我们对这类化合物作为潜在抑制剂分支酸变位酶 (MtbCM) 的兴趣，这是识别抗结核药物的已知目标，我们报告了在超声照射下快速构建 4(3 H )-喹唑啉酮环。目前的声化学方法涉及碘介导的 2-氨基苯甲酰胺或其衍生物与在 DMSO 水溶液中容易获得的醇在超声下发生的反应。一系列4（3 H)-喹唑啉酮衍生物制备，其中取代基如芳基或杂芳基环或烷基或苯乙烯基部分可以存在于产物的C-2位置。还使用这种声化学方法制备了喹唑啉酮的类似物，例如 pteridin-4(3 H )-one 和 pyrido[2,3 - d ]pyrimidin-4(3 H )-one 衍生物。一般而言，当产物的C-2取代基为芳烃部分时，可获得良好的产物收率，而在其余情况下收率可接受至适中。使用较温和的条件、廉价的碘以及
• Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
  作者：Katerina Kumpan、Amit Nathubhai、Chenlu Zhang、Pauline J. Wood、Matthew D. Lloyd、Andrew S. Thompson、Teemu Haikarainen、Lari Lehtiö、Michael D. Threadgill

  DOI：10.1016/j.bmc.2015.05.005

  日期：2015.7

  The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl) ate their target proteins using NAD(+) as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with beta-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused > 1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2. (C) 2015 Elsevier Ltd. All rights reserved.