3-(4-carboxyphenyl)-5-hydroxymethyl-1,2,4-oxadiazole | 1092400-78-6

• 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-(4-carboxyphenyl)-5-hydroxymethyl-1,2,4-oxadiazole
• 英文别名: 4-[5-(Hydroxymethyl)-1,2,4-oxadiazol-3-yl]benzoic acid
• CAS: 1092400-78-6
• 化学式: C₁₀H₈N₂O₄
• 分子量: 220.185
• InChiKey: MGZAVZFKVHETRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-chloromethyl-3-(4-methoxycarbonylphenyl)-1,2,4-oxadiazole 在 sodium hydroxide 、 水 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以68%的产率得到3-(4-carboxyphenyl)-5-hydroxymethyl-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

文献信息

• Design, Synthesis, and Biological Evaluation of <i>N</i>-Carboxyphenylpyrrole Derivatives as Potent HIV Fusion Inhibitors Targeting gp41
  作者：Kun Liu、Hong Lu、Ling Hou、Zhi Qi、Cátia Teixeira、Florent Barbault、Bo-Tao Fan、Shuwen Liu、Shibo Jiang、Lan Xie

  DOI：10.1021/jm800869t

  日期：2008.12.25

  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.