ethyl 2-(2-tert-butoxycarbonylamino)-5-(trifluoromethyl)phenyl-2-oxoacetate | 159684-37-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 2-(2-tert-butoxycarbonylamino)-5-(trifluoromethyl)phenyl-2-oxoacetate
• 英文别名: ethyl [2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(trifluoromethyl)phenyl](oxo)acetate；Ethyl 2-[[(1,1-dimethylethoxy)carbonyl]amino]-I+/--oxo-5-(trifluoromethyl)benzeneacetate；ethyl 2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(trifluoromethyl)phenyl]-2-oxoacetate
• CAS: 159684-37-4
• 化学式: C₁₆H₁₈F₃NO₅
• 分子量: 361.318
• InChiKey: YQELPWDEUURHKA-UHFFFAOYSA-N

物化性质

• 沸点：
  381.2±42.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 2-(2-tert-butoxycarbonylamino)-5-(trifluoromethyl)phenyl-2-oxoacetate 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 以89%的产率得到5-三氟甲基靛红
  参考文献：
  名称：

  合成isatins的一般方法：从苯胺制备区域特异性功能化isatins

  摘要：

  已经开发出一种新方法，用于将取代的苯胺区域特异性地转化为靛红。该方法利用邻位锂化的，受保护的苯胺衍生物与草酸二乙酯的反应来提供α-酮酸酯。氨基部分的水解脱保护伴随有环化作用以提供伊斯丁。

  DOI：

  10.1016/0040-4039(94)85299-5
• 作为产物：
  描述：

  草酸二乙酯 、 4-(三氟甲基)苯基氨基甲酸叔丁酯 在 仲丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以67%的产率得到ethyl 2-(2-tert-butoxycarbonylamino)-5-(trifluoromethyl)phenyl-2-oxoacetate
  参考文献：
  名称：

  合成isatins的一般方法：从苯胺制备区域特异性功能化isatins

  摘要：

  已经开发出一种新方法，用于将取代的苯胺区域特异性地转化为靛红。该方法利用邻位锂化的，受保护的苯胺衍生物与草酸二乙酯的反应来提供α-酮酸酯。氨基部分的水解脱保护伴随有环化作用以提供伊斯丁。

  DOI：

  10.1016/0040-4039(94)85299-5

文献信息

• [EN] TRPV4 ANTAGONISTS<br/>[FR] ANTAGONISTES DE TRPV4
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011119704A1

  公开（公告）日：2011-09-29

  The present invention relates to quinoline analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.

  本发明涉及喹啉类似物、含有它们的药物组合物以及它们作为TRPV4拮抗剂的用途。
• 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。
• 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.
• US7285558B2
  申请人：——

  公开号：US7285558B2

  公开（公告）日：2007-10-23
• A general method for the synthesis of isatins: Preparation of regiospecifically functionalized isatins from anilines
  作者：Piyasena Hewawasam、Nicholas A. Meanwell

  DOI：10.1016/0040-4039(94)85299-5

  日期：1994.10

  A new method has been developed for regiospecific conversion of substituted anilines to isatins. The method utilizes the reaction of an ortho-lithiated, protected aniline derivative with diethyl oxalate to furnish an α-ketoester. Hydrolytic deprotection of the amino moiety is accompanied by cyclization to provide the isatin.

  已经开发出一种新方法，用于将取代的苯胺区域特异性地转化为靛红。该方法利用邻位锂化的，受保护的苯胺衍生物与草酸二乙酯的反应来提供α-酮酸酯。氨基部分的水解脱保护伴随有环化作用以提供伊斯丁。