ethyl 7-chloro-1-methyl-4-oxo-1,4-dihydro-1,6-naphthyridine-3-carboxylate | 791812-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 7-chloro-1-methyl-4-oxo-1,4-dihydro-1,6-naphthyridine-3-carboxylate
• 英文别名: Ethyl 7-chloro-1-methyl-4-oxo-1,6-naphthyridine-3-carboxylate
• CAS: 791812-42-5
• 化学式: C₁₂H₁₁ClN₂O₃
• 分子量: 266.684
• InChiKey: WBMGKLCENQZEAN-UHFFFAOYSA-N

物化性质

• 熔点：
  165-168 °C
• 沸点：
  416.5±45.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 7-chloro-1-methyl-4-oxo-1,4-dihydro-1,6-naphthyridine-3-carboxylate 在 potassium hydroxide 作用下， 以 水 为溶剂， 反应 0.5h， 生成 7-chloro-1-methyl-4-oxo-1,4-dihydro-1,6-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  利用二卤代化合物的交叉偶联和S N Ar反应制备3,7-二取代的1,6-萘啶-4（1 H）-的新方法

  摘要：

  报道了一种以中等到良好的产率合成一系列3,7-二取代的1,6-萘并吡啶-4（1 H）-的新途径。该策略涉及制备3,7-二卤代化合物，该化合物使用钯催化的交叉偶联和S N Ar反应进行差分功能化。

  DOI：

  10.1016/j.tetlet.2018.08.013
• 作为产物：
  描述：

  2-(4,6-dichloronicotinoyl)-3-(dimethylamino)acrylic acid ethyl ester 在 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 2.5h， 生成 ethyl 7-chloro-1-methyl-4-oxo-1,4-dihydro-1,6-naphthyridine-3-carboxylate
  参考文献：
  名称：

  Structure Modifications of 6-Aminoquinolones with Potent Anti-HIV Activity

  摘要：

  We have recently discovered that 6-aminoquinolone derivatives could be valid leads for the development of new anti-HIV agents because of their new and diversified mode of action. In fact, studies carried out on the lead WM5 showed that this derivative is able to inhibit the Tat-mediated long terminal repeat driven transcription, an essential step in the HIV-1 replication cycle. Thus, starting from lead WM5, we performed the design and synthesis of an enlarged series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-amino derivatives to be obtained and the structure-activity relationship to be delineated. Some derivatives, 26c, 26e, 26i, and 26j, proved to be highly effective in inhibiting HIV replication at 50% inhibitory concentration in the range of 0.0087-0.7 mug/mL in MT-4, PBMCs and CEM cell lines coupled with positive selectivity indexes that reach values higher than 1000 on CEM cell lines for compounds 26e and 26i. Time-of-addition experiments clearly confirm that the new, potent 6-aminoquinolones interact at a postintegration step in the replication cycle of HIV.

  DOI：

  10.1021/jm049721p

文献信息

• Structural Investigation of the Naphthyridone Scaffold: Identification of a 1,6-Naphthyridone Derivative with Potent and Selective Anti-HIV Activity
  作者：Oriana Tabarrini、Serena Massari、Luca Sancineto、Dirk Daelemans、Stefano Sabatini、Giuseppe Manfroni、Violetta Cecchetti、Christophe Pannecouque

  DOI：10.1002/cmdc.201100073

  日期：2011.7.4

  replacement of the quinolone nucleus with a naphthyridone core was shown to be very productive. In this work, the naphthyridone scaffold was investigated in depth by synthesizing various analogues. This led to the identification of NM13 as the most selective derivative obtained in MT‐4 cells. It is the result of the successful combination of the 1,6‐naphthyridone nucleus and the C7 benzothiazolpiperazine

  在大量先前报道的具有独特作用机制的抗HIV 6-去氟喹诺酮类药物的基础上，抑制Tat介导的转录，用萘啶酮核心替代喹诺酮核被证明是非常有效的。在这项工作中，通过合成各种类似物深入研究了萘啶酮支架。这导致将NM13鉴定为MT-4细胞中获得的最具选择性的衍生物。这是1,6-萘啶酮核与C7苯并噻唑哌嗪基团成功结合的结果，这不仅首次赋予了有效的抗HIV活性，而且显示出很高的选择性。旨在对这种新衍生物的抗HIV谱进行更彻底调查的进一步研究正在进行中。
• Optimization of a Potent, Orally Active S1P₁ Agonist Containing a Quinolinone Core
  作者：Paul E. Harrington、Michael D. Croghan、Christopher Fotsch、Mike Frohn、Brian A. Lanman、Lewis D. Pennington、Alexander J. Pickrell、Anthony B. Reed、Kelvin K. C. Sham、Andrew Tasker、Heather A. Arnett、Michael Fiorino、Matthew R. Lee、Michele McElvain、Henry G. Morrison、Han Xu、Yang Xu、Xuxia Zhang、Min Wong、Victor J. Cee

  DOI：10.1021/ml200252b

  日期：2012.1.12

  The optimization of a series of SIP, agonists with limited activity against S1P(3) is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg.
• Structure Modifications of 6-Aminoquinolones with Potent Anti-HIV Activity
  作者：Oriana Tabarrini、Miguel Stevens、Violetta Cecchetti、Stefano Sabatini、Micaela Dell'Uomo、Giuseppe Manfroni、Manlio Palumbo、Christophe Pannecouque、Erik De Clercq、Arnaldo Fravolini

  DOI：10.1021/jm049721p

  日期：2004.10.1

  We have recently discovered that 6-aminoquinolone derivatives could be valid leads for the development of new anti-HIV agents because of their new and diversified mode of action. In fact, studies carried out on the lead WM5 showed that this derivative is able to inhibit the Tat-mediated long terminal repeat driven transcription, an essential step in the HIV-1 replication cycle. Thus, starting from lead WM5, we performed the design and synthesis of an enlarged series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-amino derivatives to be obtained and the structure-activity relationship to be delineated. Some derivatives, 26c, 26e, 26i, and 26j, proved to be highly effective in inhibiting HIV replication at 50% inhibitory concentration in the range of 0.0087-0.7 mug/mL in MT-4, PBMCs and CEM cell lines coupled with positive selectivity indexes that reach values higher than 1000 on CEM cell lines for compounds 26e and 26i. Time-of-addition experiments clearly confirm that the new, potent 6-aminoquinolones interact at a postintegration step in the replication cycle of HIV.
• Novel approach towards 3,7-disubstituted 1,6-naphthyridin-4(1H)-ones exploiting cross-coupling and SNAr reactions of a dihalogenated compound
  作者：Ousmane Dembélé、David Montoir、Thomas Yvorra、Dylan Sérillon、Alain Tonnerre、Muriel Duflos、Jean-Michel Robert、Marc-Antoine Bazin

  DOI：10.1016/j.tetlet.2018.08.013

  日期：2018.9

  towards the synthesis of a series of 3,7-disubstituted 1,6-naphthyridin-4(1H)-ones in moderate to good yields is reported. The strategy involves the preparation of a 3,7-dihalogenated compound that undergoes differential functionalization using palladium-catalyzed cross-coupling and SNAr reactions.

  报道了一种以中等到良好的产率合成一系列3,7-二取代的1,6-萘并吡啶-4（1 H）-的新途径。该策略涉及制备3,7-二卤代化合物，该化合物使用钯催化的交叉偶联和S N Ar反应进行差分功能化。