Ethyl 6-(trifluoromethoxy)-2-(trifluoromethyl)-2h-chromene-3-carboxylate | 1260403-33-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: Ethyl 6-(trifluoromethoxy)-2-(trifluoromethyl)-2h-chromene-3-carboxylate
• 英文别名: ethyl 6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylate
• CAS: 1260403-33-5
• 化学式: C₁₄H₁₀F₆O₄
• 分子量: 356.221
• InChiKey: ZOYXXZQFRFOHMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Ethyl 6-(trifluoromethoxy)-2-(trifluoromethyl)-2h-chromene-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 6-(trifluoromethoxy)-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylic acid
  参考文献：
  名称：

  The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: The three microdose candidates

  摘要：

  In this manuscript, we report the discovery of the substituted 2-trifluoromethyl-2H-benzopyran-3-carboxylic acids as a novel series of potent and selective cyclooxygenase-2 (COX-2) inhibitors. We provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data. The challenge of a surprisingly long half-life (t(1/2) = 360 h) of the first clinical candidate 1 and human t(1/2) had been difficult to predict based on allometric scaling for this class of highly ppb compounds. We used a microdose strategy which led to the discovery of clinical agents 18c-(S), 29b-(S), and 34b-(S) with human half-life of 57, 13, and 11 h. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.059
• 作为产物：
  描述：

  4,4,4-三氟巴豆酸乙酯 、 2-羟基-5-(三氟甲氧基)苯甲醛 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Ethyl 6-(trifluoromethoxy)-2-(trifluoromethyl)-2h-chromene-3-carboxylate
  参考文献：
  名称：

  The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: The three microdose candidates

  摘要：

  In this manuscript, we report the discovery of the substituted 2-trifluoromethyl-2H-benzopyran-3-carboxylic acids as a novel series of potent and selective cyclooxygenase-2 (COX-2) inhibitors. We provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data. The challenge of a surprisingly long half-life (t(1/2) = 360 h) of the first clinical candidate 1 and human t(1/2) had been difficult to predict based on allometric scaling for this class of highly ppb compounds. We used a microdose strategy which led to the discovery of clinical agents 18c-(S), 29b-(S), and 34b-(S) with human half-life of 57, 13, and 11 h. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.059

文献信息

• [EN] SUBSTITUTED CYCLOPROPYL CHROMENE COMPOUNDS FOR USE IN THE TREATMENT AND PREVENTION OF INFLAMMATION RELATED CONDITIONS<br/>[FR] COMPOSES DE CYCLOPROPYL CHROMENE SUBSTITUES DESTINES A ETRE UTILISES DANS LE TRAITEMENT ET LA PREVENTION DE PATHOLOGIES LIEES A DES INFLAMMATIONS
  申请人：PHARMACIA & UPJOHN CO LLC

  公开号：WO2006040672A1

  公开（公告）日：2006-04-20

  The subject invention concerns methods and compounds that have utility in the treatment of a condition associated with cyclooxygenase-2 mediated disorders. Compounds of particular interest are benzopyrans and their analogs defined by formula (1) Wherein Z, X, R1, R2, R3, and R4 are as described in the specification.

  本发明涉及在与环氧合酶-2介导的疾病相关的情况治疗中具有效用的方法和化合物。特别感兴趣的化合物是由式（1）定义的苯并吡喃和它们的类似物，其中Z、X、R1、R2、R3和R4如规范中所述。
• The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: The three microdose candidates
  作者：Jane L. Wang、Karl Aston、David Limburg、Cindy Ludwig、Ann E. Hallinan、Francis Koszyk、Bruce Hamper、David Brown、Matthew Graneto、John Talley、Timothy Maziasz、Jaime Masferrer、Jeffery Carter

  DOI：10.1016/j.bmcl.2010.07.059

  日期：2010.12

  In this manuscript, we report the discovery of the substituted 2-trifluoromethyl-2H-benzopyran-3-carboxylic acids as a novel series of potent and selective cyclooxygenase-2 (COX-2) inhibitors. We provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data. The challenge of a surprisingly long half-life (t(1/2) = 360 h) of the first clinical candidate 1 and human t(1/2) had been difficult to predict based on allometric scaling for this class of highly ppb compounds. We used a microdose strategy which led to the discovery of clinical agents 18c-(S), 29b-(S), and 34b-(S) with human half-life of 57, 13, and 11 h. (C) 2010 Elsevier Ltd. All rights reserved.