3-[4-(溴甲基)苯基]-5-[4-苯基-5-(三氟甲基)-2-噻吩基]-1,2,4-恶二唑 | 1034188-53-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-[4-(溴甲基)苯基]-5-[4-苯基-5-(三氟甲基)-2-噻吩基]-1,2,4-恶二唑
• 英文名称: 3-[4-(bromomethyl)phenyl]-5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazole
• 英文别名: 3-[4-(bromomethyl)phenyl]-5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazole
• CAS: 1034188-53-8
• 化学式: C₂₀H₁₂BrF₃N₂OS
• 分子量: 465.293
• InChiKey: WFTFBTCUSQDNDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[4-(溴甲基)苯基]-5-[4-苯基-5-(三氟甲基)-2-噻吩基]-1,2,4-恶二唑 在 potassium tert-butylate 、 lithium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 23.0h， 生成 1-[(4-{5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles

  摘要：

  The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P(1) receptors, while a variety of side effects have been ascribed to its S1P(3) receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P(1) receptor agonism. Here we describe a study of the tolerance of the S1P(1) and S1P(3) receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P(1) receptor agonists with good selectivity vs S1P(3) receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

  DOI：

  10.1021/jm5010336
• 作为产物：
  描述：

  3-[(4-羟甲基)苯基]-5-(4-苯基-5-三氟甲基-2-噻吩基)-1,2,4-恶二唑 在 N-溴代丁二酰亚胺(NBS) 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 5.5h， 生成 3-[4-(溴甲基)苯基]-5-[4-苯基-5-(三氟甲基)-2-噻吩基]-1,2,4-恶二唑
  参考文献：
  名称：

  WO2008/74820

  摘要：

  公开号：

文献信息

• OXADIAZOLE DERIVATES AS S1P1 RECEPTOR AGONISTS
  申请人：Ahmed Mahmood

  公开号：US20100048639A1

  公开（公告）日：2010-02-25

  The present invention relates to novel oxadiazole compounds of formula (I) having pharmacological activity, pharmaceutical compositions containing them and their use in the treatment of various disorders.

  本发明涉及具有药理活性的新型噁唑烷化合物（I）的制备，包含它们的制药组合物以及它们在治疗各种疾病中的应用。
• OXADIAZOLE DERIVATIVES AS S1P1 RECEPTOR AGONISTS
  申请人：Glaxo Group Limited

  公开号：EP2091950A1

  公开（公告）日：2009-08-26
• [EN] OXADIAZOLE DERIVATIVES AS S1P1 RECEPTOR AGONISTS<br/>[FR] DÉRIVÉS D'OXADIAZOLE EN TANT QU'AGONISTES DU RÉCEPTEUR S1P1
  申请人：GLAXO GROUP LTD

  公开号：WO2008074820A1

  公开（公告）日：2008-06-26

  [EN] The present invention relates to novel oxadiazole compounds of formula (I) having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.
  [FR] La présente invention concerne des composés d'oxadiazole innovants de formule (I) ayant une activité pharmacologique, leurs procédés de préparation, des compositions pharmaceutiques qui les contiennent et leur utilisation pour le traitement de diverses affections.