benzyl 3-(3-chloro-2-oxopropyl)-1H-indole-1-carboxylate | 851547-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: benzyl 3-(3-chloro-2-oxopropyl)-1H-indole-1-carboxylate
• 英文别名: 3-[1-(benzyloxycarbonyl)indol-3-yl]-1-chloropropan-2-one；benzyl 3-(3-chloro-2-oxopropyl)indole-1-carboxylate
• CAS: 851547-83-6
• 化学式: C₁₉H₁₆ClNO₃
• 分子量: 341.794
• InChiKey: LLOFYRYNSSKYBW-UHFFFAOYSA-N

物化性质

• 沸点：
  516.7±60.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl 3-(3-chloro-2-oxopropyl)-1H-indole-1-carboxylate 在 sodium hydroxide 、 三乙胺 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 12.0h， 生成 7-Bromo-3-hydroxy-2-[(1H-indol-3-yl)methyl]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：

  3-吲哚乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.5h， 生成 benzyl 3-(3-chloro-2-oxopropyl)-1H-indole-1-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

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。
• Methods and Compositions for Treatment of Scleritis and Related Disorders
  申请人：Bedard Patricia W.

  公开号：US20080125454A1

  公开（公告）日：2008-05-29

  The present teachings relate to the field of anti-inflammatory substances and more particularly to compounds that are useful for the treatment of scleritis, a scleritis symptom, or a scleritis-related disorder. In one aspect, methods of treating scleritis, a scleritis symptom, or a scleritis-related disorder generally include administering to a subject a compound of Formula I: or a pharmaceutically acceptable salt, hydrate or ester thereof, wherein W 1 , W 2 , R 1 , L, X, Y, Z, and n 1 are defined as described herein.

  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。
• Methods and Compositions for Selectin Inhibition
  申请人：Kaila Neelu

  公开号：US20090069564A1

  公开（公告）日：2009-03-12

  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，更具体地涉及一种新型化合物，其作为哺乳动物粘附蛋白选择素的拮抗剂。在某些实施例中，提供了治疗选择素介导疾病的方法，其中包括给予式I化合物的治疗，其中该式中的组分变量在此定义。
• METHODS AND COMPOSITIONS FOR SELECTIN INHIBITION
  申请人：Wyeth

  公开号：EP1682510A2

  公开（公告）日：2006-07-26
• US7465798B2
  申请人：——

  公开号：US7465798B2

  公开（公告）日：2008-12-16