4-[2-[1-Benzhydryl-5-chloro-2-[2-[[2-(trifluoromethoxy)phenyl]sulfonylamino]ethyl]indol-3-yl]ethoxy]benzoic acid | 540525-78-8

• 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: 4-[2-[1-Benzhydryl-5-chloro-2-[2-[[2-(trifluoromethoxy)phenyl]sulfonylamino]ethyl]indol-3-yl]ethoxy]benzoic acid
• CAS: 540525-78-8
• 化学式: C₃₉H₃₂ClF₃N₂O₆S
• 分子量: 749.207
• InChiKey: JKQUXYFWPPTBFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  52
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  methyl 4-(2-{5-chloro-1-(diphenylmethyl)-2-[2-({[2-(trifluoromethoxy)phenyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以90%的产率得到4-[2-[1-Benzhydryl-5-chloro-2-[2-[[2-(trifluoromethoxy)phenyl]sulfonylamino]ethyl]indol-3-yl]ethoxy]benzoic acid
  参考文献：
  名称：

  Benzenesulfonamide indole inhibitors of cytosolic phospholipase A2α: Optimization of in vitro potency and rat pharmacokinetics for oral efficacy

  摘要：

  The synthesis and structure-activity relationship of a series of benzenesulfonamide indole inhibitors of cPLA(2)alpha are described. Substitution of the benzenesulfonamide led to analogues with 50-fold improvement in potency versus the unsubstituted benzenesulfonamide lead compound. Rat pharmacokinetics in a minimal formulation was used to prioritize compounds, leading to the discovery of a potent inhibitor of cPLA(2)alpha With oral efficacy in models of rat carrageenan paw edema and Ascaris suum airway challenge in naturally sensitized sheep. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.060

文献信息

• INHIBITORS OF CYTOSOLIC PHOSPHOLIPASE A2
  申请人：Wyeth

  公开号：EP1451154B1

  公开（公告）日：2008-01-16
• Inhibitors of cytosolic phospholipase A2
  申请人：Wyeth LLC

  公开号：EP1892239B1

  公开（公告）日：2013-02-20
• US7605156B2
  申请人：——

  公开号：US7605156B2

  公开（公告）日：2009-10-20
• US7713964B2
  申请人：——

  公开号：US7713964B2

  公开（公告）日：2010-05-11
• Benzenesulfonamide indole inhibitors of cytosolic phospholipase A2α: Optimization of in vitro potency and rat pharmacokinetics for oral efficacy
  作者：Katherine L. Lee、Mark L. Behnke、Megan A. Foley、Lihren Chen、Weiheng Wang、Richard Vargas、Jill Nunez、Steve Tam、Nevena Mollova、Xin Xu

  DOI：10.1016/j.bmc.2007.10.060

  日期：2008.2.1

  The synthesis and structure-activity relationship of a series of benzenesulfonamide indole inhibitors of cPLA(2)alpha are described. Substitution of the benzenesulfonamide led to analogues with 50-fold improvement in potency versus the unsubstituted benzenesulfonamide lead compound. Rat pharmacokinetics in a minimal formulation was used to prioritize compounds, leading to the discovery of a potent inhibitor of cPLA(2)alpha With oral efficacy in models of rat carrageenan paw edema and Ascaris suum airway challenge in naturally sensitized sheep. (C) 2007 Elsevier Ltd. All rights reserved.