8-bromo-3,4-dihydro-1H-thiopyrano[4,3-b]quinolin-10(5H)-one | 1312077-70-5

• 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: 8-bromo-3,4-dihydro-1H-thiopyrano[4,3-b]quinolin-10(5H)-one
• 英文别名: 8-Bromo-1,3,4,5-tetrahydrothiopyrano[4,3-b]quinolin-10-one
• CAS: 1312077-70-5
• 化学式: C₁₂H₁₀BrNOS
• 分子量: 296.188
• InChiKey: GPLYKFFEXOENDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  8-bromo-3,4-dihydro-1H-thiopyrano[4,3-b]quinolin-10(5H)-one 、 4-氯-2-甲基苯硼酸 在 2-双环己基膦-2',6'-二甲氧基联苯 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以70%的产率得到7-(4-chloro-2-methylphenyl)-1,3,4,10-tetrahydro-2-thia-10-azaanthracen-9-one
  参考文献：
  名称：

  Optimization of 1,2,3,4-Tetrahydroacridin-9(10H)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships

  摘要：

  Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.

  DOI：

  10.1021/jm200015a
• 作为产物：
  描述：

  硫代二丙酸 在 乙醇 、 硫酸 、 sodium hydride 、 溶剂黄146 作用下， 以 乙醚 、 苯 为溶剂， 反应 12.0h， 生成 8-bromo-3,4-dihydro-1H-thiopyrano[4,3-b]quinolin-10(5H)-one
  参考文献：
  名称：

  Optimization of 1,2,3,4-Tetrahydroacridin-9(10H)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships

  摘要：

  Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC50 < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.

  DOI：

  10.1021/jm200015a