10-甲基嘧啶并[4,5-b]喹啉-2,4(3h,10h)-二酮 | 27132-53-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 10-甲基嘧啶并[4,5-b]喹啉-2,4(3h,10h)-二酮
• 中文别名: 10-甲基-5-脱氮异咯嗪
• 英文名称: 10-Methyl-5-deaza-iso-alloxazin
• 英文别名: 10-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione；10-methylpyrimido[4,5-b]quinoline-2,4-dione
• CAS: 27132-53-2
• 化学式: C₁₂H₉N₃O₂
• 分子量: 227.222
• InChiKey: VPPVXLHZEZARQZ-UHFFFAOYSA-N

物化性质

• 熔点：
  359℃ (acetic acid water )

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  10-甲基嘧啶并[4,5-b]喹啉-2,4(3h,10h)-二酮 在 叔丁基过氧化氢 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成 10-methyl-5-deazaisoalloxazine 4a,5-epoxide
  参考文献：
  名称：

  Synthesis of a 4a,5-epoxy-5-deazaflavin derivative

  摘要：

  DOI：

  10.1021/ja00519a031
• 作为产物：
  描述：

  2-amino-4-chloro-6-[methyl(phenyl)amino]pyrimidine-5-carbaldehyde 在 溶剂黄146 作用下， 反应 0.25h， 以70%的产率得到10-甲基嘧啶并[4,5-b]喹啉-2,4(3h,10h)-二酮
  参考文献：
  名称：

  微波辐射辅助直接合成嘧啶并[4,5- b ]喹啉衍生物

  摘要：

  通过N 4取代的2,4-二氨基-6-氯嘧啶-5-甲醛的微波辅助分子内环化反应，已经制备了几种嘧啶[4,5- b ]喹啉，黄素类似物。该反应在氨基和氯的水解下进行。该方法特别有价值的特征包括更宽的基板范围和操作简便性，以及用于小规模高速合成的更高的安全性。

  DOI：

  10.1016/j.tetlet.2009.12.114
• 作为试剂：
  描述：

  苯甲醇 在 potassium carbonate 、 10-甲基嘧啶并[4,5-b]喹啉-2,4(3h,10h)-二酮 作用下， 反应 1.0h， 以39%的产率得到苯甲醛
  参考文献：
  名称：

  Kuroda, Kazunori; Nagamatus, Tomohisa; Sakuma, Yoshiharu, Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 929 - 931

  摘要：

  DOI：

文献信息

• METHODS, COMPOUNDS, COMPOSITIONS AND VEHICLES FOR DELIVERING 3-AMINO-1-PROPANESULFONIC ACID
  申请人：Kong Xianqi

  公开号：US20080146642A1

  公开（公告）日：2008-06-19

  The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compounds that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to, the prevention and treatment of Alzheimer's disease.

  这项发明涉及用于在受试者中（最好是人类受试者）传递3-氨基-1-丙磺酸（3APS）的方法、化合物、组合物和载体。该发明涵盖将产生或生成3APS的化合物，无论是在体外还是体内。首选的化合物包括3APS的氨基酸前药，用于预防和治疗阿尔茨海默病等用途。
• Antitumor studies. Part 3: Design, synthesis, antitumor activity, and molecular docking study of novel 2-methylthio-, 2-amino-, and 2-(N-substituted amino)-10-alkyl-2-deoxo-5-deazaflavins
  作者：Hamed I. Ali、Noriyuki Ashida、Tomohisa Nagamatsu

  DOI：10.1016/j.bmc.2007.06.058

  日期：2007.10

  have been synthesized by reaction of 6-(N-alkylanilino)-2-methylthiopyrimidin-4(3H)-ones with Vilsmeier reagent. The similar 2-(N-substituted amino) derivatives were prepared by nucleophilic replacement reaction of the 2-methylthio moiety by appropriate amines. The 2-oxo derivatives (i.e., 5-deazaflavins) were obtained by acidic hydrolysis of the 2-methylthio derivatives. The antitumor activities

  通过使6-（N-烷基苯胺基）-2-甲基硫代嘧啶-4（3H）-与Vilsmeier试剂反应合成了各种新颖的10-烷基-2-脱氧-2-甲基硫基5-脱氮黄素。通过2-甲硫基部分与适当的胺的亲核取代反应制备相似的2-（N-取代的氨基）衍生物。通过2-甲基硫代衍生物的酸水解获得2-氧代衍生物（即5-脱氮黄素）。在体外已经研究了针对CCRF-HSB-2和KB细胞的抗肿瘤活性以及针对HSV-1和HSV-2的抗病毒活性，并且许多化合物显示出有希望的抗肿瘤活性。此外，已完成将AutoDock分子对接至PTK中的功能，以优化这些化合物作为潜在PTK抑制剂的可能性。然而，
• Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid
  申请人：BHI Limited Partnership

  公开号：EP2862581A2

  公开（公告）日：2015-04-22

  The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1 -propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compounds that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to, the prevention and treatment of Alzheimer's disease.

  本发明涉及向受试者（最好是人类受试者）提供 3-氨基-1-丙磺酸（3APS）的方法、化合物、组合物和载体。本发明包括在体外或体内产生或生成 3APS 的化合物。优选的化合物包括 3APS 的氨基酸原药，其用途包括但不限于预防和治疗阿尔茨海默病。
• Toxoflavins and Deazaflavins as the First Reported Selective Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase II
  作者：Ali Raoof、Paul Depledge、Niall M. Hamilton、Nicola S. Hamilton、James R. Hitchin、Gemma V. Hopkins、Allan M. Jordan、Laura A. Maguire、Alison E. McGonagle、Daniel P. Mould、Mathew Rushbrooke、Helen F. Small、Kate M. Smith、Graeme J. Thomson、Fabrice Turlais、Ian D. Waddell、Bohdan Waszkowycz、Amanda J. Watson、Donald J. Ogilvie

  DOI：10.1021/jm400568p

  日期：2013.8.22

  The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAP.) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.
• 5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2
  作者：Michael P. Dickens、Patricia Roxburgh、Andreas Hock、Mokdad Mezna、Barrie Kellam、Karen H. Vousden、Peter M. Fischer

  DOI：10.1016/j.bmc.2013.09.038

  日期：2013.11

  Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e. g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.