5-bromomethyl-3-(4-methoxycarbonylphenyl)-1,2,4-oxadiazole | 1092400-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-bromomethyl-3-(4-methoxycarbonylphenyl)-1,2,4-oxadiazole
• 英文别名: Methyl 4-[5-(bromomethyl)-1,2,4-oxadiazol-3-yl]benzoate
• CAS: 1092400-74-2
• 化学式: C₁₁H₉BrN₂O₃
• 分子量: 297.108
• InChiKey: NPVQVHHRNFJNJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-bromomethyl-3-(4-methoxycarbonylphenyl)-1,2,4-oxadiazole 在 水 、 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 12.0h， 以65%的产率得到5-bromomethyl-3-(4-carboxyphenyl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of N-Carboxyphenylpyrrole Derivatives as Potent HIV Fusion Inhibitors Targeting gp41

  摘要：

  On the basis of the structures of small-molecule hits targeting the HIV-1 gp41, N-(4-carboxy-3-hydi-oxy)plieiiyl-2,5-dimethylpyl-role (2, NB-2), and N-(3-carboxy-4-chloro)phenylpyrrole (A(1), NB-64), 42 N-carboxyphenylpyrrole derivatives in two categories (A and B series) were designed and synthesized. We found that I I compounds exhibited promising anti-HIV-1 activity at micromolar level and their antiviral activity was correlated with their inhibitory activity on gp41 six-helix bundle formation, suggesting that these compounds block HIV fusion and entry by disrupting gp41 core formation. The structure-activity relationship and molecular docking analysis revealed that the carboxyl group Could interact with either Arg579 or Lys574 to form salt bridges and two methyl groups on the pyrrole ring were favorable for interaction with the residues in gp41 pocket. The most active compound, N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole (A(12)), partially occupied the deep hydrophobic pocket, suggesting that enlarging the molecular size of A(12) could improve its binding affinity and anti-HIV-1 activity for further development as a small-molecule HIV fusion and entry inhibitor.

  DOI：

  10.1021/jm800869t
• 作为产物：
  描述：

  溴乙酰溴 、 4-[(z)-氨基(羟基亚氨基)甲基]苯甲酸甲酯 以 四氢呋喃 为溶剂， 反应 8.0h， 以64%的产率得到5-bromomethyl-3-(4-methoxycarbonylphenyl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of N-Carboxyphenylpyrrole Derivatives as Potent HIV Fusion Inhibitors Targeting gp41

  摘要：

  On the basis of the structures of small-molecule hits targeting the HIV-1 gp41, N-(4-carboxy-3-hydi-oxy)plieiiyl-2,5-dimethylpyl-role (2, NB-2), and N-(3-carboxy-4-chloro)phenylpyrrole (A(1), NB-64), 42 N-carboxyphenylpyrrole derivatives in two categories (A and B series) were designed and synthesized. We found that I I compounds exhibited promising anti-HIV-1 activity at micromolar level and their antiviral activity was correlated with their inhibitory activity on gp41 six-helix bundle formation, suggesting that these compounds block HIV fusion and entry by disrupting gp41 core formation. The structure-activity relationship and molecular docking analysis revealed that the carboxyl group Could interact with either Arg579 or Lys574 to form salt bridges and two methyl groups on the pyrrole ring were favorable for interaction with the residues in gp41 pocket. The most active compound, N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole (A(12)), partially occupied the deep hydrophobic pocket, suggesting that enlarging the molecular size of A(12) could improve its binding affinity and anti-HIV-1 activity for further development as a small-molecule HIV fusion and entry inhibitor.

  DOI：

  10.1021/jm800869t