9-chloro-6-trifluoromethyl-1,2,3,4-tetrahydro-acridine | 66949-85-7

• 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: 9-chloro-6-trifluoromethyl-1,2,3,4-tetrahydro-acridine
• 英文别名: 9-Chloro-6-(trifluoromethyl)-1,2,3,4-tetrahydroacridine
• CAS: 66949-85-7
• 化学式: C₁₄H₁₁ClF₃N
• 分子量: 285.696
• InChiKey: TXHKGGJEGBBTGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-chloro-6-trifluoromethyl-1,2,3,4-tetrahydro-acridine 在 溶剂黄146 作用下， 生成 6-trifluoromethyl-1,2,3,4-tetrahydroacridin-9(10H)-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：

  2-氨基-4-三氟甲基苯甲酸甲酯 在 sodium hydroxide 、 三氯氧磷 作用下， 以 水 为溶剂， 生成 9-chloro-6-trifluoromethyl-1,2,3,4-tetrahydro-acridine
  参考文献：
  名称：

  Discovery of Novel Tacrine–Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer’s Disease

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c00160

文献信息

• Discovery of Novel Tacrine–Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer’s Disease
  作者：Hong Yao、Giuseppe Uras、Pengfei Zhang、Shengtao Xu、Ying Yin、Jie Liu、Shuai Qin、Xinuo Li、Stephanie Allen、Renren Bai、Qi Gong、Haiyan Zhang、Zheying Zhu、Jinyi Xu

  DOI：10.1021/acs.jmedchem.1c00160

  日期：2021.6.10
• Optimization of 1,2,3,4-Tetrahydroacridin-9(10<i>H</i>)-ones as Antimalarials Utilizing Structure–Activity and Structure–Property Relationships
  作者：R. Matthew Cross、Jordany R. Maignan、Tina S. Mutka、Lisa Luong、Justin Sargent、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm200015a

  日期：2011.7.14

  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.