2-(4-chloro-benzyl)-3-hydroxy-8-phenyl-quinoline-4-carboxylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 2-(4-chloro-benzyl)-3-hydroxy-8-phenyl-quinoline-4-carboxylic acid
• 英文别名: 2-[(4-chlorophenyl)methyl]-3-hydroxy-8-phenylquinoline-4-carboxylic acid
• 化学式: C₂₃H₁₆ClNO₃
• 分子量: 389.838
• InChiKey: VCJXSDQEVNAXAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-chloro-benzyl)-3-hydroxy-8-phenyl-quinoline-4-carboxylic acid 、 7-甲基靛红 、 1-(乙酰氧基)-3-(4-氯苯基)-2-丙酮 在 crude acid 作用下， 以to give Compound 6 as a bright yellow powder (0.774 g, 38% yield)的产率得到2-(4-chlorobenzyl)-3-hydroxy-8-methylquinoline-4-carboxylicacid
  参考文献：
  名称：

  Methods and Compositions for Selectin Inhibition

  摘要：

  本发明涉及抗炎物质领域，更具体地涉及新型化合物，其作为哺乳动物粘附蛋白（称为选择素）拮抗剂。在某些实施例中，提供了用于治疗选择素介导的疾病的方法，其中包括给予式I化合物的给药，其中组成变量在此定义。

  公开号：

  US20090076077A1
• 作为产物：
  描述：

  对氯苯乙酸 在 氢氧化钾 、 草酰氯 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 9.0h， 生成 2-(4-chloro-benzyl)-3-hydroxy-8-phenyl-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

• Methods and compositions for selectin inhibition
  申请人：Kaila Neelu

  公开号：US20050101568A1

  公开（公告）日：2005-05-12

  The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I: wherein the constituent variables are defined herein.

  本发明涉及抗炎物质领域，更特别地涉及作为哺乳动物粘附蛋白拮抗剂的新化合物。在某些实施例中，提供了治疗选择素介导疾病的方法，包括给予式I的化合物： 其中组分变量在此处定义。
• METHODS AND COMPOSITIONS FOR SELECTIN INHIBITION
  申请人：Wyeth

  公开号：EP1682511A2

  公开（公告）日：2006-07-26
• US7465799B2
  申请人：——

  公开号：US7465799B2

  公开（公告）日：2008-12-16
• [EN] METHODS AND COMPOSITIONS FOR SELECTIN INHIBITION<br/>[FR] METHODES ET COMPOSITIONS POUR INHIBER LA SELECTINE
  申请人：WYETH CORP

  公开号：WO2005047257A2

  公开（公告）日：2005-05-26

  The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula: (I) wherein the constituent variables are defined herein.