1-(3,4-dichlorobenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-ol | 1203564-72-0

• 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: 1-(3,4-dichlorobenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-ol
• 英文别名: 1-[(3,4-Dichlorophenyl)methyl]-2,2,4-trimethylquinolin-6-ol
• CAS: 1203564-72-0
• 化学式: C₁₉H₁₉Cl₂NO
• 分子量: 348.272
• InChiKey: GGRAPNPKTUBODL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3,4-dichlorobenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-ol 、 乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以97%的产率得到1-(3,4-dichlorobenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate
  参考文献：
  名称：

  Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives

  摘要：

  The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1, 2-dlhydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 mu M against these parasites and a selectivity index or 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (> 14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.

  DOI：

  10.1021/jm900723w
• 作为产物：
  描述：

  2,2,4-三甲基-1,2-二氢-喹啉-6-醇 、 3,4-二氯氯苄 在 三乙胺 作用下， 以 甲苯 为溶剂， 以57%的产率得到1-(3,4-dichlorobenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-ol
  参考文献：
  名称：

  Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives

  摘要：

  The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1, 2-dlhydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 mu M against these parasites and a selectivity index or 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (> 14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.

  DOI：

  10.1021/jm900723w

文献信息

• Antitrypanosomal Activity of 1,2-Dihydroquinolin-6-ols and Their Ester Derivatives
  作者：Jean Fotie、Marcel Kaiser、Dawn A. Delfín、Joshua Manley、Carolyn S. Reid、Jean-Marc Paris、Tanja Wenzler、Louis Maes、Kiran V. Mahasenan、Chenglong Li、Karl A. Werbovetz

  DOI：10.1021/jm900723w

  日期：2010.2.11

  The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1, 2-dlhydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 mu M against these parasites and a selectivity index or 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (> 14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.