4-[3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl]butanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-[3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl]butanoic acid
• 英文别名: 4-(3-Naphthalen-1-yl-1,2,4-oxadiazol-5-yl)butanoic acid
• 化学式: C₁₆H₁₄N₂O₃
• 分子量: 282.299
• InChiKey: KAPXSXPDLAKJTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl]butanoic acid 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以79%的产率得到sodium 4-[3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl]butanoate
  参考文献：
  名称：

  Discovery of 1,2,4-oxadiazole derivatives as a novel class of noncompetitive inhibitors of 3-hydroxykynurenine transaminase (HKT) from Aedes aegypti

  摘要：

  The mosquito Aedes aegypti is the vector of arboviruses such as Zika, Chikungunya, dengue and yellow fever. These infectious diseases have a major impact on public health. The unavailability of effective vaccines or drugs to prevent or treat most of these diseases makes vector control the main form of prevention. One strategy to promote mosquito population control is the use of synthetic insecticides to inhibit key enzymes in the metabolic pathway of these insects, particularly during larval stages. One of the main targets of the kynurenine detoxification pathway in mosquitoes is the enzyme 3-hydroxykynurenine transaminase (HKT), which catalyzes the conversion of 3-hydroxykynurenine (3-HK) into xanthurenic acid (XA). In this work, we report eleven newly synthesized oxadiazole derivatives and demonstrate that these compounds are potent noncompetitive inhibitors of HKT from Ae. aegypti. The present data provide direct evidence that HKT can be explored as a molecular target for the discovery of novel larvicides against Ae. aegypti. More importantly, it ensures that structural information derived from the HKT 3D-structure can be used to guide the development of more potent inhibitors.

  DOI：

  10.1016/j.bmc.2019.115252
• 作为产物：
  描述：

  氰基萘 在 盐酸羟胺 、 sodium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 生成 4-[3-(naphthalen-2-yl)-1,2,4-oxadiazol-5-yl]butanoic acid
  参考文献：
  名称：

  Discovery of 1,2,4-oxadiazole derivatives as a novel class of noncompetitive inhibitors of 3-hydroxykynurenine transaminase (HKT) from Aedes aegypti

  摘要：

  The mosquito Aedes aegypti is the vector of arboviruses such as Zika, Chikungunya, dengue and yellow fever. These infectious diseases have a major impact on public health. The unavailability of effective vaccines or drugs to prevent or treat most of these diseases makes vector control the main form of prevention. One strategy to promote mosquito population control is the use of synthetic insecticides to inhibit key enzymes in the metabolic pathway of these insects, particularly during larval stages. One of the main targets of the kynurenine detoxification pathway in mosquitoes is the enzyme 3-hydroxykynurenine transaminase (HKT), which catalyzes the conversion of 3-hydroxykynurenine (3-HK) into xanthurenic acid (XA). In this work, we report eleven newly synthesized oxadiazole derivatives and demonstrate that these compounds are potent noncompetitive inhibitors of HKT from Ae. aegypti. The present data provide direct evidence that HKT can be explored as a molecular target for the discovery of novel larvicides against Ae. aegypti. More importantly, it ensures that structural information derived from the HKT 3D-structure can be used to guide the development of more potent inhibitors.

  DOI：

  10.1016/j.bmc.2019.115252

文献信息

• Discovery of 1,2,4-oxadiazole derivatives as a novel class of noncompetitive inhibitors of 3-hydroxykynurenine transaminase (HKT) from Aedes aegypti
  作者：Larissa G. Maciel、Andrew A. Oliveira、Tatiany P. Romão、Laylla L.L. Leal、Rafael V.C. Guido、Maria Helena N.L. Silva-Filha、Janaína V. dos Anjos、Thereza A. Soares

  DOI：10.1016/j.bmc.2019.115252

  日期：2020.1

  The mosquito Aedes aegypti is the vector of arboviruses such as Zika, Chikungunya, dengue and yellow fever. These infectious diseases have a major impact on public health. The unavailability of effective vaccines or drugs to prevent or treat most of these diseases makes vector control the main form of prevention. One strategy to promote mosquito population control is the use of synthetic insecticides to inhibit key enzymes in the metabolic pathway of these insects, particularly during larval stages. One of the main targets of the kynurenine detoxification pathway in mosquitoes is the enzyme 3-hydroxykynurenine transaminase (HKT), which catalyzes the conversion of 3-hydroxykynurenine (3-HK) into xanthurenic acid (XA). In this work, we report eleven newly synthesized oxadiazole derivatives and demonstrate that these compounds are potent noncompetitive inhibitors of HKT from Ae. aegypti. The present data provide direct evidence that HKT can be explored as a molecular target for the discovery of novel larvicides against Ae. aegypti. More importantly, it ensures that structural information derived from the HKT 3D-structure can be used to guide the development of more potent inhibitors.