N-(4-methoxyphenyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-amine | 1257257-01-4

• 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: N-(4-methoxyphenyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-amine
• 英文别名: N-(4-methoxyphenyl)-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-amine
• CAS: 1257257-01-4
• 化学式: C₁₆H₁₂F₃N₃O₂
• 分子量: 335.285
• InChiKey: UNZROOVCILNHKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(4-methoxyphenyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-amine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以31%的产率得到4-(((5-(4-trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)amino)phenol
  参考文献：
  名称：

  [EN] ENZYME INTERACTING AGENTS
  [FR] AGENTS D'INTERACTION AVEC DES ENZYMES

  摘要：

  本公开涉及一般性地，但不仅限于化合物及其用作酶相互作用剂的用途，特别是与鞘脂类生物合成途径中的一个或多个酶相互作用的剂。本公开进一步涉及将这些化合物用作研究工具、治疗用途、包含所述化合物的组合物和剂，以及使用这些化合物进行治疗的方法。

  公开号：

  WO2015196258A1
• 作为产物：
  描述：

  4-三氟甲基苯甲酸 、 4-(4-甲氧基苯基)-3-硫代氨基甲酰肼 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以63%的产率得到N-(4-methoxyphenyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  Discovery of Novel GSK-3β Inhibitors with Potent in Vitro and in Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-Based Virtual Screening

  摘要：

  Dysregulation of glycogen synthase kinase (GSK-3 beta) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3 beta yielded, from among compounds in our in-house database and two commercial databases, new GSK-3 beta inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.

  DOI：

  10.1021/jm100941j

文献信息

• [EN] ENZYME INTERACTING AGENTS<br/>[FR] AGENTS D'INTERACTION AVEC DES ENZYMES
  申请人：UNIV MONASH

  公开号：WO2015196258A1

  公开（公告）日：2015-12-30

  The present disclosure relates generally, but not exclusively, to compounds and their use as enzyme interacting agents, in particular, agents which interact with one or more enzymes in the sphingolipid biosynthesis pathway. The disclosure further relates to the use of such 5 compounds as research tools, use in therapy, to compositions and agents comprising said compounds, and to methods of treatment using said compounds.

  本公开涉及一般性地，但不仅限于化合物及其用作酶相互作用剂的用途，特别是与鞘脂类生物合成途径中的一个或多个酶相互作用的剂。本公开进一步涉及将这些化合物用作研究工具、治疗用途、包含所述化合物的组合物和剂，以及使用这些化合物进行治疗的方法。
• ENZYME INTERACTING AGENTS
  申请人：Monash University

  公开号：EP3160949A1

  公开（公告）日：2017-05-03
• US9828351B2
  申请人：——

  公开号：US9828351B2

  公开（公告）日：2017-11-28
• From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure–Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)
  作者：Luigi Aurelio、Carmen V. Scullino、Melissa R. Pitman、Anna Sexton、Victoria Oliver、Lorena Davies、Richard J. Rebello、Luc Furic、Darren J. Creek、Stuart M. Pitson、Bernard L. Flynn

  DOI：10.1021/acs.jmedchem.5b01439

  日期：2016.2.11

  The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results using this pharmacological agent are complicated by several factors: poor SK1/2 selectivity, additional activity as an inducer of SK1-degradation, and off-target effects, including its recently identified capacity to inhibit dihydroceramide desaturase-1 (Des1). In this study, we have delineated the structure-activity relationship (SAR) for these different targets and correlated them to that required for anticancer activity and determined that Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. In the course of these efforts, a series of novel SK1, SK2, and Des1 inhibitors have been generated, including compounds with significantly greater anticancer activity.
• Discovery of Novel GSK-3β Inhibitors with Potent in Vitro and in Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-Based Virtual Screening
  作者：Mohammad A. Khanfar、Ronald A. Hill、Amal Kaddoumi、Khalid A. El Sayed

  DOI：10.1021/jm100941j

  日期：2010.12.23

  Dysregulation of glycogen synthase kinase (GSK-3 beta) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3 beta yielded, from among compounds in our in-house database and two commercial databases, new GSK-3 beta inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.