3-hydroxy-2-indan-2-yl-8-(trifluoromethyl)quinoline-4-carboxylic acid | 1065501-87-2

• 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-2-indan-2-yl-8-(trifluoromethyl)quinoline-4-carboxylic acid
• 英文别名: 2-(2,3-dihydro-1H-inden-2-yl)-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid
• CAS: 1065501-87-2
• 化学式: C₂₀H₁₄F₃NO₃
• 分子量: 373.331
• InChiKey: AWNVQTZGVXYSBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(2,3-dihydro-1H-inden-2-yl)-2-hydroxyethan-1-one 、 7-三氟甲基靛红 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以16.1%的产率得到3-hydroxy-2-indan-2-yl-8-(trifluoromethyl)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

文献信息

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

  公开号：US20080242700A1

  公开（公告）日：2008-10-02

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

  本教学涉及到式I的化合物： 其中组成变量在此定义。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。提供了治疗选择素介导的疾病的方法，其中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：EP2132180A1

  公开（公告）日：2009-12-16
• [EN] METHODS AND COMPOSITIONS FOR SELECTIN INHIBITION<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR INHIBITION DE SÉLECTINE
  申请人：WYETH CORP

  公开号：WO2008121805A1

  公开（公告）日：2008-10-09

  [EN] The present teachings relate to compounds of formula I: wherein the constituent variables are defined herein. Compounds of the present teachings can act as antagonists of the mammalian adhesion proteins known as selectins. Methods for treating selectin mediated disorders are provided, which include administration of these compounds in a therapeutically effective amount.
  [FR] La présente invention concerne des composés de formule I : dans laquelle les variables de constituant sont définies ici. Les composés de la présente invention peuvent agir comme antagonistes de protéines d'adhésion mammifères connues comme étant des sélectines. Des procédés de traitement de troubles véhiculés par la sélectine sont proposés, lesdits procédés comprennent l'administration de ces composés en une quantité efficace du point de vue thérapeutique.
• 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
  作者：Adrian Huang、Alessandro Moretto、Kristin Janz、Michael Lowe、Patricia W. Bedard、Steve Tam、Li Di、Valerie Clerin、Natalia Sushkova、Boris Tchernychev、Desiree H. H. Tsao、James C. Keith、Gray D. Shaw、Robert G. Schaub、Qin Wang、Neelu Kaila

  DOI：10.1021/jm9013696

  日期：2010.8.26

  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.