N'-hydroxy-3-methoxy-4-phenylmethoxybenzenecarboximidamide | 1017022-14-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N'-hydroxy-3-methoxy-4-phenylmethoxybenzenecarboximidamide
• CAS: 1017022-14-8
• 化学式: C₁₅H₁₆N₂O₃
• 分子量: 272.304
• InChiKey: YGVVNAHCCSQTSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  77.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  烟酰氯 、 N'-hydroxy-3-methoxy-4-phenylmethoxybenzenecarboximidamide 在 吡啶 、 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以64%的产率得到2-methoxy-4-(5-(pyridin-3-yl)-1,2,4-oxadiazol-3-yl)phenol
  参考文献：
  名称：

  Diaryl-1,2,4-oxadiazole antioxidants: Synthesis and properties of inhibiting the oxidation of DNA and scavenging radicals

  摘要：

  Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit (OH)-O-center dot-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu2+/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+center dot)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.biochi.2012.12.005
• 作为产物：
  描述：

  3-羟基-4-苄氧基苯甲醛 在 甲酸 、 盐酸羟胺 、 sodium formate 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 N'-hydroxy-3-methoxy-4-phenylmethoxybenzenecarboximidamide
  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 and anticancer activities of novel 3,5-disubstituted-1,2,4-oxadiazoles
  作者：Dalip Kumar、Gautam Patel、Emmanuel O. Johnson、Kavita Shah

  DOI：10.1016/j.bmcl.2009.03.158

  日期：2009.5

  A series of 3,5-disubstituted-1,2,4-oxadiazoles were synthesized and evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Formation of 1,2,4-oxadiazole ring was accomplished by the reaction of amidoxime with carboxylic acids. The in vitro cytotoxic effects of 3,5-disubstituted-1,2,4-oxadiazoles have been demonstrated across a wide array of tumor cell types and

  合成了一系列3,5-二取代-1,2,4-恶二唑，并评估了它们对各种癌细胞的体外抗增殖活性。1,2,4-恶二唑环的形成是通过of胺肟与羧酸的反应完成的。已在多种肿瘤细胞类型中证明了3,5-二取代-1,2,4-恶二唑的体外细胞毒性作用，一些化合物对胰腺（3f，3h，3j和3k）和前列腺具有特异性（3n）癌细胞。在制备的3,5-二取代-1,2,4-恶二唑中，化合物3n的选择性最高（> 450倍），化合物3p 对前列腺癌细胞系具有最大的细胞毒性（10 nM）。
• 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.
• Diaryl-1,2,4-oxadiazole antioxidants: Synthesis and properties of inhibiting the oxidation of DNA and scavenging radicals
  作者：Chao Zhao、Zai-Qun Liu

  DOI：10.1016/j.biochi.2012.12.005

  日期：2013.4

  Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit (OH)-O-center dot-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu2+/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+center dot)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant. (C) 2012 Elsevier Masson SAS. All rights reserved.