(E)-tert-butyl 3-(6-chloro-7-methoxy-2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)acrylate | 1248347-18-3

• 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: (E)-tert-butyl 3-(6-chloro-7-methoxy-2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)acrylate
• 英文别名: tert-butyl (E)-3-(6-chloro-7-methoxy-2-methyl-4-oxo-1H-quinolin-3-yl)prop-2-enoate
• CAS: 1248347-18-3
• 化学式: C₁₈H₂₀ClNO₄
• 分子量: 349.814
• InChiKey: RKGYVWAKNRSOJG-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  丙烯酸叔丁酯 、 4-(benzyloxy)-3-bromo-6-chloro-7-methoxy-2-methylquinoline 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2-(dicyclohexylphoshphino)-2',4',6'-triisopropyl-1,1'-biphenyl 、 三乙胺 作用下， 以 甲苯 为溶剂， 以96%的产率得到(E)-tert-butyl 3-(6-chloro-7-methoxy-2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)acrylate
  参考文献：
  名称：

  Endochin Optimization: Structure−Activity and Structure−Property Relationship Studies of 3-Substituted 2-Methyl-4(1H)-quinolones with Antimalarial Activity

  摘要：

  Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of mullidrug resistant W2 and TM90-C2B isolates of Plasmodium folciparum. Follow-up structure activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.

  DOI：

  10.1021/jm1007903

文献信息

• Endochin Optimization: Structure−Activity and Structure−Property Relationship Studies of 3-Substituted 2-Methyl-4(1<i>H</i>)-quinolones with Antimalarial Activity
  作者：R. Matthew Cross、Andrii Monastyrskyi、Tina S. Mutka、Jeremy N. Burrows、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm1007903

  日期：2010.10.14

  Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of mullidrug resistant W2 and TM90-C2B isolates of Plasmodium folciparum. Follow-up structure activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.