3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid | 924633-55-6

• 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: 3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid
• CAS: 924633-55-6
• 化学式: C₁₁H₆F₃NO₃
• 分子量: 257.169
• InChiKey: DTMSBEXXPDMQKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 3-羟基-8-(三氟甲基)喹啉-4-羧酸甲酯
  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 盐酸 、 氢氧化钾 、 硫酸 、 盐酸羟胺 、 sodium sulfate 作用下， 生成 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

文献信息

• Bromodecarboxylation of Quinoline Salicylic Acids: Increasing the Diversity of Accessible Substituted Quinolines
  作者：Kristin Janz、Neelu Kaila

  DOI：10.1021/jo9018232

  日期：2009.11.20

  Quinoline salicylic acids underwent bromodecarboxylation at room temperature upon treatment with N-bromosuccinimide. A wide variety of functional groups was tolerated. Several one-pot transformations were also carried out, allowing the preparation of diverse 4-substituted quinolines.

  在用N-溴代琥珀酰亚胺处理后，喹啉水杨酸在室温下进行溴脱羧。可以容忍各种各样的功能基团。还进行了几次一锅转化，从而制备了多种4-取代的喹啉。
• 2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[<i>H</i>]quinoline-4-carboxylic Acid (PSI-697):  Identification of a Clinical Candidate from the Quinoline Salicylic Acid Series of P-Selectin Antagonists
  作者：Neelu Kaila、Kristin Janz、Adrian Huang、Alessandro Moretto、Silvano DeBernardo、Patricia W. Bedard、Steve Tam、Valerie Clerin、James C. Keith、Desirée H. H. Tsao、Natalia Sushkova、Gray D. Shaw、Raymond T. Camphausen、Robert G. Schaub、Qin Wang

  DOI：10.1021/jm060631p

  日期：2007.1.1

  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.