tert-butyl 4-(3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate | 1312793-85-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 4-(3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate
• 英文别名: t-butyl 4-(3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidin-1-carboxylate；Tert-butyl 4-[3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate
• CAS: 1312793-85-3
• 化学式: C₂₁H₂₉N₃O₅
• 分子量: 403.478
• InChiKey: KBGDQNHOGJFALY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  86.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以78%的产率得到3-(3-ethoxy-4-methoxyphenyl)-5-(piperidin-4-yl)-1,2,4-oxadiazole
  参考文献：
  名称：

  新型1,2,4-恶二唑及其类似物的合成作为潜在的抗癌药

  摘要：

  合成了3,5-二取代-1,2,4-恶二唑7–9及其生物等效物1,3,4-恶二唑14和1,3,4-噻二唑16的文库，并对其体外抗癌性进行了评估。对一组六种人类癌细胞系的潜力。合成恶二唑7–9的关键步骤包括将of胺肟6与适当的羧酸偶联，然后进行热环化。由常见的前体二酰基肼13的反应制备生物甾体1,3,4-恶二唑14和1,3,4-噻二唑16分别使用亚硫酰氯和Lawesson试剂。对合成化合物的抗癌研究表明，在C-3芳基环上存在环戊氧基或正丁氧基，在1,2,4-恶二唑的C-5位置上存在哌啶-4-基或三氯甲基是必不可少的。活动。尤其是1,2,4-恶二唑7i和类似物1,3,4-噻二唑16分别显示出对DU145（IC 50：9.3μM）和MDA-MB-231（IC 50：9.2μM）细胞系的显着活性。。

  DOI：

  10.1016/j.ejmech.2011.03.031
• 作为产物：
  描述：

  3-羟基-4-甲氧基苯腈 在 盐酸羟胺 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 tert-butyl 4-(3-(3-ethoxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Design and Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2

  摘要：

  A series of 3,5‐disubstituted‐1,2,4‐oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5‐disubstituted‐1,2,4‐oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50 = 5.28 μm). Structure–activity relationship studies of 3,5‐disubstituted‐1,2,4‐oxadiazoles revealed that substituents 3‐cyclopentyloxy‐4‐methoxyphenyl group at 3‐position and cyclic ring bearing heteroatoms at 5‐position are important for activity. Molecular modeling study of the 3,5‐disubstituted‐1,2,4‐oxadiazoles with PDE4B has shown similar interactions of 3‐cyclopentyloxy‐4‐methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3‐(3‐Cyclopentyloxy‐4‐methoxyphenyl)‐5‐(piperidin‐4‐yl)‐1,2,4‐oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin‐induced pain in mice and carrageenan‐induced paw edema model in rat.

  DOI：

  10.1111/j.1747-0285.2011.01304.x

文献信息

• Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents
  作者：Dalip Kumar、Gautam Patel、Angela K. Chavers、Kuei-Hua Chang、Kavita Shah

  DOI：10.1016/j.ejmech.2011.03.031

  日期：2011.7

  A library of 3,5-disubstituted-1,2,4-oxadiazoles 7–9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of oxadiazoles 7–9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres

  合成了3,5-二取代-1,2,4-恶二唑7–9及其生物等效物1,3,4-恶二唑14和1,3,4-噻二唑16的文库，并对其体外抗癌性进行了评估。对一组六种人类癌细胞系的潜力。合成恶二唑7–9的关键步骤包括将of胺肟6与适当的羧酸偶联，然后进行热环化。由常见的前体二酰基肼13的反应制备生物甾体1,3,4-恶二唑14和1,3,4-噻二唑16分别使用亚硫酰氯和Lawesson试剂。对合成化合物的抗癌研究表明，在C-3芳基环上存在环戊氧基或正丁氧基，在1,2,4-恶二唑的C-5位置上存在哌啶-4-基或三氯甲基是必不可少的。活动。尤其是1,2,4-恶二唑7i和类似物1,3,4-噻二唑16分别显示出对DU145（IC 50：9.3μM）和MDA-MB-231（IC 50：9.2μM）细胞系的显着活性。。
• Design and Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2
  作者：Dalip Kumar、Gautam Patel、Lalitha Vijayakrishnan、Sunanda G. Dastidar、Abhijit Ray

  DOI：10.1111/j.1747-0285.2011.01304.x

  日期：2012.5

  A series of 3,5‐disubstituted‐1,2,4‐oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5‐disubstituted‐1,2,4‐oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50 = 5.28 μm). Structure–activity relationship studies of 3,5‐disubstituted‐1,2,4‐oxadiazoles revealed that substituents 3‐cyclopentyloxy‐4‐methoxyphenyl group at 3‐position and cyclic ring bearing heteroatoms at 5‐position are important for activity. Molecular modeling study of the 3,5‐disubstituted‐1,2,4‐oxadiazoles with PDE4B has shown similar interactions of 3‐cyclopentyloxy‐4‐methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3‐(3‐Cyclopentyloxy‐4‐methoxyphenyl)‐5‐(piperidin‐4‐yl)‐1,2,4‐oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin‐induced pain in mice and carrageenan‐induced paw edema model in rat.