2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h]quinoline-4-carboxylic acid | 851546-61-7

• 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: 2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h]quinoline-4-carboxylic acid
• 英文别名: PSI-697；2-(4-Chloro-benzyl)-3-hydroxy-7,8,9,10-tetrahydro-benzo[h]quinoline-4-carboxylic acid；2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydro-benzo[h]quinoline-4-carboxylic acid；2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo(H)quinoline-4-carboxylic acid；2-[(4-chlorophenyl)methyl]-3-hydroxy-7,8,9,10-tetrahydrobenzo[h]quinoline-4-carboxylic acid
• CAS: 851546-61-7
• 化学式: C₂₁H₁₈ClNO₃
• 分子量: 367.832
• InChiKey: DIEPFYNZGUUVHD-UHFFFAOYSA-N

物化性质

• 沸点：
  553.0±50.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥ 45.8 mg/mL（124.51 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8℃

制备方法与用途

PSI-697是一种P-selectin抑制剂。

反应信息

• 作为反应物：
  描述：

  2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h]quinoline-4-carboxylic acid 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 19.0h， 生成 2-[(4-Chlorophenyl)methyl]-3-phenylmethoxy-7,8,9,10-tetrahydrobenzo[h]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：

  6,7,8,9-四氢-1H-苯并[g]吲哚-2,3-二酮 在 氢氧化钾 、 水 作用下， 以 乙醇 为溶剂， 反应 4.08h， 生成 2-(4-chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[h]quinoline-4-carboxylic acid
  参考文献：
  名称：

  Methods and Compositions for Treatment of Scleritis and Related Disorders

  摘要：

  目前的教导涉及抗炎物质领域，更具体地涉及对用于治疗巩膜炎、巩膜炎症状或与巩膜炎相关疾病有用的化合物。在一个方面，治疗巩膜炎、巩膜炎症状或巩膜炎相关疾病的方法通常包括向受试者施用公式I的化合物： 或其药用可接受的盐、水合物或酯，其中W 1 ，W 2 ，R 1 ，L，X，Y，Z和n 1 的定义如本文所述。

  公开号：

  US20080125454A1

文献信息

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

  公开号：US20050101569A1

  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： 其中组分变量在此定义。
• [EN] HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS MODIFICATEURS D'HÉMOGLOBINE ET LEURS UTILISATIONS
  申请人：FRONTHERA U S PHARMACEUTICALS LLC

  公开号：WO2017218960A1

  公开（公告）日：2017-12-21

  Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.

  本文描述了化合物，包括其药用可接受的盐，制备这些化合物的方法，包含这些化合物的药物组合物，以及使用这些化合物治疗、预防或诊断基于血液的疾病、紊乱或状况的方法。
• Methods and Compositions for Selectin Inhibition
  申请人：Kaila Neelu

  公开号：US20080255192A1

  公开（公告）日：2008-10-16

  The present teachings relate to novel compounds of formula I: wherein the constituent variables are as defined herein. Compounds of the present teachings can act as antagonists of the mammalian adhesion proteins known as selecting. Methods for treating or preventing selectin-mediated disorders are provided, which include administration of these compounds in a therapeutically effective amount.

  本教学涉及到式I的新化合物： 其中组成变量如本文所定义。本教学的化合物可以作为被称为选择素的哺乳动物粘附蛋白的拮抗剂。提供了治疗或预防选择素介导的疾病的方法，包括以治疗有效剂量给予这些化合物。
• Process for the synthesis of compounds for selectin inhibition
  申请人：Wang Youchu

  公开号：US20070082923A1

  公开（公告）日：2007-04-12

  The present teachings relate to the field of anti-inflammatory substances, and more particularly to the preparation of compounds that act as antagonists of the mammalian adhesion proteins known as selecting. In some embodiments, the present teachings provide methods for preparing compounds for treating selectin-mediated disorders that have the formula VI: wherein R 1 , R 2 , R 3 , p, and q are defined herein.

  本教学涉及抗炎物质领域，更具体地涉及制备作为哺乳动物粘附蛋白拮抗剂的化合物。在某些实施例中，本教学提供了制备用于治疗选择素介导疾病的化合物的方法，其具有以下公式 VI：其中R1、R2、R3、p 和 q 在此处被定义。
• Process for preparing isatins with control of side-product formation
  申请人：Wilk Kazimierz Bogdan

  公开号：US20060247442A1

  公开（公告）日：2006-11-02

  Methods and kits for preventing or minimizing the formation of isatin oximes during formation of an isatin from an isonitrosoacetanilide are provided. Also provided are methods and kits for preventing or minimizing the formation of isatin oxime impurities after formation of an isatin from an isonitrosoacetanilide by using a decoy agent in the quenching and/or extraction steps. The isatins can be prepared using a decoy agent and desirably a strong acid. Further provided are methods for preparing isatin oximes.

  提供了一种防止或最小化在从异硝基乙酰苯胺制备异吲哚时形成异吲哚肟的方法和试剂盒。还提供了一种使用诱饵剂在淬灭和/或提取步骤中防止或最小化从异硝基乙酰苯胺制备异吲哚后形成异吲哚肟杂质的方法和试剂盒。可以使用诱饵剂和强酸制备异吲哚。还提供了制备异吲哚肟的方法。