3-(5-isobutyl-1,2,4-oxadiazol-3-yl)phenol | 10185-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-isobutyl-1,2,4-oxadiazol-3-yl)phenol
• 英文别名: 3-m-Hydroxphenyl-5-isobutyl-1,2,4-oxadiazol；3-[5-(2-Methylpropyl)-1,2,4-oxadiazol-3-yl]phenol
• CAS: 10185-82-7
• 化学式: C₁₂H₁₄N₂O₂
• mdl: MFCD10689457
• 分子量: 218.255
• InChiKey: QAIRQHRISBPFTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-甲基-4-氯-2-吡啶甲酰胺 、 3-(5-isobutyl-1,2,4-oxadiazol-3-yl)phenol 以 neat (no solvent) 为溶剂， 反应 90.0h， 以25%的产率得到4-(3-(5-isobutyl-1,2,4-oxadiazol-3-yl)phenoxy)-N-methylpicolinamide
  参考文献：
  名称：

  3-Aryl-1,2,4-oxadiazole Derivatives Active Against Human Rhinovirus

  摘要：

  The human rhinovirus (hRV) is the causative agent of the common cold that often aggravates respiratory complications in patients with asthma or chronic obstructive pulmonary disease. The high rate of mutations and variety of serotypes are limiting the development of anti-hRV drugs, which emphasizes the need for the discovery of novel lead compounds. Previously, we identified antiviral compound 1 that we used here as the starting material for developing a novel compound series with high efficacy against hRV-A and -B. Improved metabolic stability was achieved by substituting an ester moiety with a 1,2,4-oxadiazole group. Specifically, compound 3k exhibited a high efficacy against hRV-B14, hRV-A21, and hRV-A71, with EC50 values of 66.0, 22.0, and 3.7 nM, respectively, and a relevant hepatic stability (59.6 and 40.7% compound remaining after 30 min in rat and human liver microsomes, respectively). An in vivo study demonstrated that 3k possessed a desirable pharmacokinetic profile with low systemic clearance (0.158 L.h(-1).Kg(-1)) and modest oral bioavailability (27.8%). Hence, 3k appears to be an interesting candidate for the development of antiviral lead compounds.

  DOI：

  10.1021/acsmedchemlett.8b00134
• 作为产物：
  描述：

  3-氰基苯酚 在 吡啶 、 羟胺 作用下， 以 水 为溶剂， 反应 32.0h， 生成 3-(5-isobutyl-1,2,4-oxadiazol-3-yl)phenol
  参考文献：
  名称：

  3-Aryl-1,2,4-oxadiazole Derivatives Active Against Human Rhinovirus

  摘要：

  The human rhinovirus (hRV) is the causative agent of the common cold that often aggravates respiratory complications in patients with asthma or chronic obstructive pulmonary disease. The high rate of mutations and variety of serotypes are limiting the development of anti-hRV drugs, which emphasizes the need for the discovery of novel lead compounds. Previously, we identified antiviral compound 1 that we used here as the starting material for developing a novel compound series with high efficacy against hRV-A and -B. Improved metabolic stability was achieved by substituting an ester moiety with a 1,2,4-oxadiazole group. Specifically, compound 3k exhibited a high efficacy against hRV-B14, hRV-A21, and hRV-A71, with EC50 values of 66.0, 22.0, and 3.7 nM, respectively, and a relevant hepatic stability (59.6 and 40.7% compound remaining after 30 min in rat and human liver microsomes, respectively). An in vivo study demonstrated that 3k possessed a desirable pharmacokinetic profile with low systemic clearance (0.158 L.h(-1).Kg(-1)) and modest oral bioavailability (27.8%). Hence, 3k appears to be an interesting candidate for the development of antiviral lead compounds.

  DOI：

  10.1021/acsmedchemlett.8b00134

文献信息

• 3-Aryl-1,2,4-oxadiazole Derivatives Active Against Human Rhinovirus
  作者：Jinwoo Kim、Jin Soo Shin、Sunjoo Ahn、Soo Bong Han、Young-Sik Jung

  DOI：10.1021/acsmedchemlett.8b00134

  日期：2018.7.12

  The human rhinovirus (hRV) is the causative agent of the common cold that often aggravates respiratory complications in patients with asthma or chronic obstructive pulmonary disease. The high rate of mutations and variety of serotypes are limiting the development of anti-hRV drugs, which emphasizes the need for the discovery of novel lead compounds. Previously, we identified antiviral compound 1 that we used here as the starting material for developing a novel compound series with high efficacy against hRV-A and -B. Improved metabolic stability was achieved by substituting an ester moiety with a 1,2,4-oxadiazole group. Specifically, compound 3k exhibited a high efficacy against hRV-B14, hRV-A21, and hRV-A71, with EC50 values of 66.0, 22.0, and 3.7 nM, respectively, and a relevant hepatic stability (59.6 and 40.7% compound remaining after 30 min in rat and human liver microsomes, respectively). An in vivo study demonstrated that 3k possessed a desirable pharmacokinetic profile with low systemic clearance (0.158 L.h(-1).Kg(-1)) and modest oral bioavailability (27.8%). Hence, 3k appears to be an interesting candidate for the development of antiviral lead compounds.