3-benzyl-5-chloropyrido[2,3-g]quinoxalin-2(1H)-one | 1037303-28-8

• 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
• 英文名称: 3-benzyl-5-chloropyrido[2,3-g]quinoxalin-2(1H)-one
• 英文别名: 3-benzyl-5-chloropyrido[3,2-g]quinoxalin-2(1H)-one；3-benzyl-5-chloro-1,2-dihydropyrido[2,3-g]quinoxalin-2-one；3-benzyl-5-chloro-1H-pyrido[2,3-g]quinoxalin-2-one
• CAS: 1037303-28-8
• 化学式: C₁₈H₁₂ClN₃O
• 分子量: 321.766
• InChiKey: FRKBQYUCDGUINM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-benzyl-5-chloropyrido[2,3-g]quinoxalin-2(1H)-one 、 硫酸二甲酯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以26%的产率得到3-benzyl-5-chloro-1-methylpyrido[2,3-g]quinoxalin-2(1H)-one
  参考文献：
  名称：

  Synthesis, cytotoxicity and antiviral evaluation of new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives

  摘要：

  Linear aromatic N-tricyclic compounds with promising antiviral activity and minimal cytotoxicity were prepared and analyzed in the last years. Specifically, the pyrido[2,3-g]quinoxalinone nucleus was found endowed with high potency against several pathogenic RNA viruses as etiological agents of important veterinary and human pathologies. Following our research program on new antiviral agents we have designed, synthesized and assayed new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives. Lead compounds 1-4 were further modified to enhance their antiviral activity and reduce their cytotoxicity. Thus, different substituents were introduced on N atom at position 1 or the 0 atom at position 2 of the leads; contextually, several groups were inserted on the nitrogen atom at position 7 of diaminoquinoline intermediates. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against RNA virus families containing single-stranded (either positive-sense (ssRNA+) or negative-sense (ssRNA-)), and double-stranded genomes (dsRNA), and against two representatives of DNA virus families. Some derivatives emerged as potential leads for further development as antiviral agents against some viruses of public health significance, such as RSV, Reo, BVDV and HCV. Particularly, compounds 4, 11b, 11c, 13c, 15a,18 and 21 resulted active against BVDV at concentrations ranging from 1.3 to 5 mu M. Compound 21 was also evaluated for its activity on the BVDV RdRp. Compound 4 was also tested as potential anti-HCV compound in a subgenomic replication assay. Molecular simulation results provided a molecular rationale for the anti-BVDV activity of these compounds. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.002
• 作为产物：
  描述：

  sodium phenylphyruvate 、 8-氯喹啉-6,7-二胺 在 硫酸 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以66%的产率得到3-benzyl-5-chloropyrido[2,3-g]quinoxalin-2(1H)-one
  参考文献：
  名称：

  喹啉三环衍生物。设计，合成和评估三种新型的RNA依赖性RNA聚合酶抑制剂的抗病毒活性

  摘要：

  在这项研究中，合成了三类新的线性N-三环化合物，它们是由喹啉核与1,2,3-三唑，咪唑或吡嗪缩合而得到的，获得了三唑并[4,5- g ]喹啉，咪唑并[4]。分别是，5-5- g喹啉和吡啶并[2，3- g ]喹喔啉。标题化合物中的细胞毒性和抗病毒活性的基于细胞的测定中测试抗RNA病毒代表三个属的的黄病毒科家族，即BVDV（瘟病毒），YFV（黄病毒属）和HCV（丙型肝炎病毒属）。喹啉衍生物也针对含有单链，无论正义（单链RNA其他RNA病毒科的代表测试+）或负义（RNA - ，和双链基因组（双链RNA），以及针对两个代表） DNA病毒家族。尽管对CVB-5，Reo-1和RSV具有选择性活性，但一些喹啉类药物显示中等程度的活性。但是，属于所有类别的衍生物均显示出对BVDV的活性。最有效的是双三唑并喹啉1m，咪唑并喹啉2e和2h以及吡啶并喹喔啉4h，4j和5n（EC 50范围1-5μM）。当在复制子

  DOI：

  10.1016/j.bmc.2011.10.009

文献信息

• WO2008/81266
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] COMPOUNDS FOR THE TREATMENT OR PREVENTION OF INFECTION BY FLAVIVIRIDAE<br/>[FR] COMPOSÉS DESTINÉS AU TRAITEMENT OU À LA PRÉVENTION D'UNE INFECTION PAR DES FLAVIVIRIDAE
  申请人：CARTA ANTONIO

  公开号：WO2008081266A1

  公开（公告）日：2008-07-10

  [EN] The present invention provides compounds, pharmaceutically acceptable derivatives thereof and pharmaceutical compositions that are useful as Flaviviridae replication inhibitors.
  [FR] La présente invention concerne des composés, des dérivés pharmaceutiquement acceptables de ceux-ci et des compositions pharmaceutiques, qui sont utiles en tant qu'inhibiteurs de la réplication des Flaviviridae.
• Quinoline tricyclic derivatives. Design, synthesis and evaluation of the antiviral activity of three new classes of RNA-dependent RNA polymerase inhibitors
  作者：Antonio Carta、Irene Briguglio、Sandra Piras、Paola Corona、Giampiero Boatto、Maria Nieddu、Paolo Giunchedi、Maria Elena Marongiu、Gabriele Giliberti、Filippo Iuliano、Sylvain Blois、Cristina Ibba、Bernardetta Busonera、Paolo La Colla

  DOI：10.1016/j.bmc.2011.10.009

  日期：2011.12

  CVB-5, Reo-1 and RSV. However, derivatives belonging to all classes showed activity against BVDV. Among the most potent were the bis-triazoloquinoline 1m, the imidazoquinolines 2e and 2h, and the pyridoquinoxalines 4h, 4j and 5n (EC50 range 1–5 μM). When tested in a replicon assay, compound 2h was the sole derivative to also display anti-HCV activity (EC50 = 3.1 μM). In enzyme assays, 1m, 2h, 5m and 5n

  在这项研究中，合成了三类新的线性N-三环化合物，它们是由喹啉核与1,2,3-三唑，咪唑或吡嗪缩合而得到的，获得了三唑并[4,5- g ]喹啉，咪唑并[4]。分别是，5-5- g喹啉和吡啶并[2，3- g ]喹喔啉。标题化合物中的细胞毒性和抗病毒活性的基于细胞的测定中测试抗RNA病毒代表三个属的的黄病毒科家族，即BVDV（瘟病毒），YFV（黄病毒属）和HCV（丙型肝炎病毒属）。喹啉衍生物也针对含有单链，无论正义（单链RNA其他RNA病毒科的代表测试+）或负义（RNA - ，和双链基因组（双链RNA），以及针对两个代表） DNA病毒家族。尽管对CVB-5，Reo-1和RSV具有选择性活性，但一些喹啉类药物显示中等程度的活性。但是，属于所有类别的衍生物均显示出对BVDV的活性。最有效的是双三唑并喹啉1m，咪唑并喹啉2e和2h以及吡啶并喹喔啉4h，4j和5n（EC 50范围1-5μM）。当在复制子
• Synthesis, cytotoxicity and antiviral evaluation of new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives
  作者：Irene Briguglio、Roberta Loddo、Erik Laurini、Maurizio Fermeglia、Sandra Piras、Paola Corona、Paolo Giunchedi、Elisabetta Gavini、Giuseppina Sanna、Gabriele Giliberti、Cristina Ibba、Pamela Farci、Paolo La Colla、Sabrina Pricl、Antonio Carta

  DOI：10.1016/j.ejmech.2015.10.002

  日期：2015.11

  Linear aromatic N-tricyclic compounds with promising antiviral activity and minimal cytotoxicity were prepared and analyzed in the last years. Specifically, the pyrido[2,3-g]quinoxalinone nucleus was found endowed with high potency against several pathogenic RNA viruses as etiological agents of important veterinary and human pathologies. Following our research program on new antiviral agents we have designed, synthesized and assayed new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives. Lead compounds 1-4 were further modified to enhance their antiviral activity and reduce their cytotoxicity. Thus, different substituents were introduced on N atom at position 1 or the 0 atom at position 2 of the leads; contextually, several groups were inserted on the nitrogen atom at position 7 of diaminoquinoline intermediates. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against RNA virus families containing single-stranded (either positive-sense (ssRNA+) or negative-sense (ssRNA-)), and double-stranded genomes (dsRNA), and against two representatives of DNA virus families. Some derivatives emerged as potential leads for further development as antiviral agents against some viruses of public health significance, such as RSV, Reo, BVDV and HCV. Particularly, compounds 4, 11b, 11c, 13c, 15a,18 and 21 resulted active against BVDV at concentrations ranging from 1.3 to 5 mu M. Compound 21 was also evaluated for its activity on the BVDV RdRp. Compound 4 was also tested as potential anti-HCV compound in a subgenomic replication assay. Molecular simulation results provided a molecular rationale for the anti-BVDV activity of these compounds. (C) 2015 Elsevier Masson SAS. All rights reserved.