3-羟基异噁唑-5-甲酰胺 | 14016-01-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-羟基异噁唑-5-甲酰胺
• 英文名称: 5-carbamoyl-3-isoxazolol
• 英文别名: 3-Hydroxyisoxazole-5-carboxamide；3-oxo-1,2-oxazole-5-carboxamide
• CAS: 14016-01-4
• 化学式: C₄H₄N₂O₃
• 分子量: 128.087
• InChiKey: VAXZHEOQJVBMQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-benzyloxy-5-carbamoylisoxazole 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 24.0h， 以74%的产率得到3-羟基异噁唑-5-甲酰胺
  参考文献：
  名称：

  4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors

  摘要：

  The insect GABA receptor (GABAR), which-is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol, analogues; were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas Synthesized analogues did, not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement Of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in Compounds that exhibited significantly enhanced antagonism with IC50 value in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 mu M analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed Competitive antagonism, with IC50 values of 30, 34, 1:07, and 96 mu M in the ac, bc, ad, and bd variants, respectively, and exhibited Moderate insecticidal activity against houseflies, with an LD50, value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs.

  DOI：

  10.1021/acs.jafc.5b01843

文献信息

• 4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors
  作者：Genyan Liu、Fumiyo Ozoe、Kenjiro Furuta、Yoshihisa Ozoe

  DOI：10.1021/acs.jafc.5b01843

  日期：2015.7.22

  The insect GABA receptor (GABAR), which-is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol, analogues; were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas Synthesized analogues did, not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement Of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in Compounds that exhibited significantly enhanced antagonism with IC50 value in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 mu M analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed Competitive antagonism, with IC50 values of 30, 34, 1:07, and 96 mu M in the ac, bc, ad, and bd variants, respectively, and exhibited Moderate insecticidal activity against houseflies, with an LD50, value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs.