7-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)indoline-2,3-dione | 851520-00-8

• 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: 7-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)indoline-2,3-dione
• 英文别名: 7-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-1H-indole-2,3-dione；7-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1H-indole-2,3-dione
• CAS: 851520-00-8
• 化学式: C₁₁H₅F₆NO₃
• 分子量: 313.156
• InChiKey: LDUYOIBCOSZQQP-UHFFFAOYSA-N

物化性质

• 密度：
  1.665±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  7-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)indoline-2,3-dione 、 2-oxo-2-(1-phenylcyclopropyl)ethyl acetate 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以30%的产率得到8-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-hydroxy-2-(1-phenylcyclopropyl)quinoline-4-carboxylic acid
  参考文献：
  名称：

  Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic Acid (PSI-421), a P-Selectin Inhibitor with Improved Pharmacokinetic Properties and Oral Efficacy in Models of Vascular Injury

  摘要：

  Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure activity-studies in this series by branching at the alpha position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.

  DOI：

  10.1021/jm9013696
• 作为产物：
  描述：

  2-imino-N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-acetamide 在 硫酸 作用下， 反应 0.17h， 生成 7-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)indoline-2,3-dione
  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。

  公开号：

  US20050101568A1

文献信息

• 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。
• METHODS AND COMPOSITIONS FOR SELECTIN INHIBITION
  申请人：Wyeth

  公开号：EP1682511A2

  公开（公告）日：2006-07-26
• QUINOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM FOR SELECTIN INHIBITION
  申请人：Wyeth

  公开号：EP2134692A2

  公开（公告）日：2009-12-23
• 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.