Zgwatinib | 1268264-10-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Zgwatinib
• 英文别名: 3-(4-methylpiperazin-1-yl)-N-(3-nitrobenzyl)-7-(trifluoromethyl)quinolin-5-amine；3-(4-methylpiperazin-1-yl)-5-(3-nitrobenzylamino)-7-(trifluoromethyl)quinoline；SOMG-833；3-(4-methylpiperazin-1-yl)-N-[(3-nitrophenyl)methyl]-7-(trifluoromethyl)quinolin-5-amine
• CAS: 1268264-10-3
• 化学式: C₂₂H₂₂F₃N₅O₂
• 分子量: 445.444
• InChiKey: JIYPGFPFAVEPFX-UHFFFAOYSA-N

物化性质

• 沸点：
  589.3±50.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-bromo-5-nitro-7-trifluoromethylquinoline 在 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 铁粉 、 氯化铵 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 9.0h， 生成 Zgwatinib
  参考文献：
  名称：

  Synthesis and c-Met Kinase Inhibition of 3,5-Disubstituted and 3,5,7-Trisubstituted Quinolines: Identification of 3-(4-Acetylpiperazin-1-yl)-5-(3-nitrobenzylamino)-7- (trifluoromethyl)quinoline as a Novel Anticancer Agent

  摘要：

  By use of an improved synthetic strategy, a series of 3,5-disubstituted and 3,5,7-trisubstituted quinolines were readily prepared. 3,5,7-Trisubstituted quinolines 21a-c, 211, and 27a-c were identified as the most potent c-Met inhibitors with IC50 of less than 1.0 nM. Compound 21b showed the most promising overall PK profile and has high potency and extraordinary selectivity to c-Met against c-Met family member Ron and 12 other tyrosine kinases. It produced constitutive inhibition of c-Met phosphorylation in c-Met dependent cell lines. At doses of 100 mg/kg, compound 21b showed statistically significant tumor growth inhibition (68-69%) in both NIH-3T3-TPR-Met and U-87 MG human gliobastoma xenograft models. These results clearly indicated that compound 21b is a potent and highly selective c-Met inhibitor. Its favorable in vitro and in vivo profiles warrant further investigation.

  DOI：

  10.1021/jm101340q

文献信息

• Expeditious one-pot synthesis of C3-piperazinyl-substituted quinolines: key precursors to potent c-Met inhibitors
  作者：Yuanxiang Wang、Jing Ai、Gang Liu、Meiyu Geng、Ao Zhang

  DOI：10.1039/c1ob05830d

  日期：——

  An effective one-pot synthesis of quinolines bearing diverse C3-piperazinyl functions was developed by using a modified Friedländer's protocol. The method not only enables the synthesis of our early reported c-Met inhibitor on a large scale, but also provides a way to generate novel multi-substituted quinolines for further structure–activity relationship (SAR) study.

  一种有效的单锅合成具有多样化C3-哌嗪基团的喹啉的方法被开发出来，采用了改进的Friedländer反应。该方法不仅能够大规模合成我们早期报道的c-Met抑制剂，还为生成新型多取代喹啉提供了一种途径，以便进一步进行结构-活性关系（SAR）研究。
• Synthesis and c-Met Kinase Inhibition of 3,5-Disubstituted and 3,5,7-Trisubstituted Quinolines: Identification of 3-(4-Acetylpiperazin-1-yl)-5-(3-nitrobenzylamino)-7- (trifluoromethyl)quinoline as a Novel Anticancer Agent
  作者：Yuanxiang Wang、Jing Ai、Ying Wang、Yi Chen、Lu Wang、Gang Liu、Meiyu Geng、Ao Zhang

  DOI：10.1021/jm101340q

  日期：2011.4.14

  By use of an improved synthetic strategy, a series of 3,5-disubstituted and 3,5,7-trisubstituted quinolines were readily prepared. 3,5,7-Trisubstituted quinolines 21a-c, 211, and 27a-c were identified as the most potent c-Met inhibitors with IC50 of less than 1.0 nM. Compound 21b showed the most promising overall PK profile and has high potency and extraordinary selectivity to c-Met against c-Met family member Ron and 12 other tyrosine kinases. It produced constitutive inhibition of c-Met phosphorylation in c-Met dependent cell lines. At doses of 100 mg/kg, compound 21b showed statistically significant tumor growth inhibition (68-69%) in both NIH-3T3-TPR-Met and U-87 MG human gliobastoma xenograft models. These results clearly indicated that compound 21b is a potent and highly selective c-Met inhibitor. Its favorable in vitro and in vivo profiles warrant further investigation.