5-(3-Chloro-thiophen-2-yl)-3-(4-chloro-phenyl)-[1,2,4]-oxadiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(3-Chloro-thiophen-2-yl)-3-(4-chloro-phenyl)-[1,2,4]-oxadiazole
• 英文别名: 3-(4-Chlorophenyl)-5-(3-chlorothiophen-2-yl)-1,2,4-oxadiazole
• 化学式: C₁₂H₆Cl₂N₂OS
• 分子量: 297.164
• InChiKey: QZRBEJJCGIGWEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-氯-N-羟基苯羧酰亚胺 、 3-氯噻吩-2-甲酰氯 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以85%的产率得到5-(3-Chloro-thiophen-2-yl)-3-(4-chloro-phenyl)-[1,2,4]-oxadiazole
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of 3-Aryl-5-aryl-1,2,4-oxadiazoles as a New Series of Apoptosis Inducers and Potential Anticancer Agents

  摘要：

  We have identified 5-(3-chlorothiophen-2-yl)-3-(4-trifluoromethylphenyl)-1,2,4-oxadiazole (1d) as a novel apoptosis inducer through our caspase- and cell-based high-throughput screening assay. Compound 1d has good activity against several breast and colorectal cancer cell lines but is inactive against several other cancer cell lines. In a flow cytometry assay, treatment of T47D cells with 1d resulted in arrest of cells in the G, phase, followed by induction of apoptosis. SAR studies of 1d showed that the 3-phenyl group can be replaced by a pyridyl group, and a substituted five-member ring in the 5-position is important for activity. 5-(3-Chlorothiophen-2-yl)-3-(5-chloropyridin-2-yl)-1,2,4-oxadiazole (41) has been found to have in vivo activity in a MX-1 tumor model. Using a photoaffinity agent, the molecular target has been identified as TIP47, an IGF II receptor binding protein. Therefore, our cell-based chemical genetics approach for the discovery of apoptosis inducers can identify potential anticancer agents as well as their molecular targets.

  DOI：

  10.1021/jm050292k

文献信息

• Substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：——

  公开号：US20030045546A1

  公开（公告）日：2003-03-06

  The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: 1 wherein Ar 1 , Ar 3 , A, B and D are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及取代的3-芳基-5-芳基-[1,2,4]-噁二唑及其类似物，由以下式I表示： 1 其中Ar1，Ar3，A，B和D在此处定义。本发明还涉及发现具有式I的化合物是caspase的激活剂和凋亡诱导剂。因此，本发明的caspase激活剂和凋亡诱导剂可用于诱导在各种临床病况中发生未受控制的异常细胞生长和扩散的细胞死亡。
• Methods of treating diseases responsive to Induction of Apoptosis
  申请人：Kasibhatla Shailaja

  公开号：US20050004005A1

  公开（公告）日：2005-01-06

  The present invention pertains to a method of treating, preventing or ameliorating a disease responsive to induction of the caspase cascade in an animal, comprising administering to the animal a compound which binds specifically to a Tail Interacting Protein Related Apoptosis Inducing Protein (TIPRAIP). The present invention also relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using TIPRAIP as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogenous binding assays using purified or partially purified TIPRAIP; or whole cell assays using cells with altered levels of TIPRAIP. The invention also contemplates use of 3-(4-azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole or a substituted 3-aryl-5-aryl-[1,2,4]-oxadiazole which bind TIPRAIP and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled 3-(4-azidophenyl)-5-(3-chloro-thiophen-2-yl)-[1,2,4]-oxadiazole (or a labeled substituted 3-aryl-5-aryl-[1,2,4]-oxadiazole) is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.

  本发明涉及一种用于治疗、预防或改善对Caspase级联诱导敏感的动物疾病的方法，包括向动物投药一种与尾部相互作用蛋白相关凋亡诱导蛋白（TIPRAIP）特异结合的化合物。本发明还涉及有用于药物发现凋亡诱导化合物的筛选方法。特别是，筛选方法涉及使用TIPRAIP作为靶标，以发现作为抗癌剂有用的凋亡激活剂。本发明的筛选方法可以采用使用纯化或部分纯化的TIPRAIP的均相或异相结合分析；或使用具有改变TIPRAIP水平的细胞的全细胞分析。本发明还考虑使用3-（4-偶氮苯基）-5-（3-氯噻吩-2-基）-[1,2,4]-噁二唑或结合TIPRAIP的取代3-芳基-5-芳基-[1,2,4]-噁二唑，可用于制备有用于药物发现的抗体。或者，标记的3-（4-偶氮苯基）-5-（3-氯噻吩-2-基）-[1,2,4]-噁二唑（或标记的取代的3-芳基-5-芳基-[1,2,4]-噁二唑）可用于药物发现的竞争结合分析。这种分析为化学文库的高通量筛选提供了凋亡激活剂。
• SUBSTITUTED 3-ARYL-5-ARYL- 1,2,4]-OXADIAZOLES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1406632A2

  公开（公告）日：2004-04-14
• EP1618205A2
  申请人：——

  公开号：EP1618205A2

  公开（公告）日：2006-01-25
• EP1618205A4
  申请人：——

  公开号：EP1618205A4

  公开（公告）日：2009-04-08