Methyl 2-(4-chloroanilino)-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylate | 924633-58-9

• 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: Methyl 2-(4-chloroanilino)-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylate
• CAS: 924633-58-9
• 化学式: C₁₈H₁₂ClF₃N₂O₃
• 分子量: 396.753
• InChiKey: XPWUUCVPGRKGKB-UHFFFAOYSA-N

物化性质

• 沸点：
  455.5±45.0 °C(Predicted)
• 密度：
  1.499±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Methyl 2-(4-chloroanilino)-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 生成 2-(4-Chlorophenylamino)-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid
  参考文献：
  名称：

  2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic Acid (PSI-697):  Identification of a Clinical Candidate from the Quinoline Salicylic Acid Series of P-Selectin Antagonists

  摘要：

  P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.

  DOI：

  10.1021/jm060631p
• 作为产物：
  描述：

  邻氨基三氟甲苯 在 palladium diacetate 、 2-(二环己基膦基)联苯 盐酸 、 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 草酰氯 、 硫酸 、 盐酸羟胺 、 caesium carbonate 、 sodium sulfate 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲苯 、 叔丁醇 为溶剂， 反应 6.0h， 生成 Methyl 2-(4-chloroanilino)-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylate
  参考文献：
  名称：

  2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic Acid (PSI-697):  Identification of a Clinical Candidate from the Quinoline Salicylic Acid Series of P-Selectin Antagonists

  摘要：

  P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.

  DOI：

  10.1021/jm060631p