N¹-(4-chlorophenyl)-N²-(1-ethyl-1H-pyrazol-4-yl)oxalamide | 1375736-76-7

• 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
• 英文名称: N¹-(4-chlorophenyl)-N²-(1-ethyl-1H-pyrazol-4-yl)oxalamide
• 英文别名: N-(4-chlorophenyl)-N'-(1-ethylpyrazol-4-yl)oxamide
• CAS: 1375736-76-7
• 化学式: C₁₃H₁₃ClN₄O₂
• 分子量: 292.725
• InChiKey: CJPBMMGQRUICSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(4-氯苯基)-2-氧代甘氨酸乙酯 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 N¹-(4-chlorophenyl)-N²-(1-ethyl-1H-pyrazol-4-yl)oxalamide
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1

  摘要：

  The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1.

  DOI：

  10.1021/jm3002247

文献信息

• Design, Synthesis, and Antiviral Activity of Entry Inhibitors That Target the CD4-Binding Site of HIV-1
  作者：Francesca Curreli、Spreeha Choudhury、Ilya Pyatkin、Victor P. Zagorodnikov、Anna Khulianova Bulay、Andrea Altieri、Young Do Kwon、Peter D. Kwong、Asim K. Debnath

  DOI：10.1021/jm3002247

  日期：2012.5.24

  The CD4 binding site on HIV-1 gp120 has been validated as a drug target to prevent HIV-1 entry to cells. Previously, we identified two small molecule inhibitors consisting of a 2,2,6,6-tetramethylpiperidine ring linked by an oxalamide to a p-halide-substituted phenyl group, which target this site, specifically, a cavity termed "Phe43 cavity". Here we use synthetic chemistry, functional assessment, and structure-based analysis to explore variants of each region of these inhibitors for improved antiviral properties. Alterations of the phenyl group and of the oxalamide linker indicated that these regions were close to optimal in the original lead compounds. Design of a series of compounds, where the tetramethylpiperidine ring was replaced with new scaffolds, led to improved antiviral activity. These new scaffolds provide insight into the surface chemistry at the entrance of the cavity and offer additional opportunities by which to optimize further these potential-next-generation therapeutics and microbicides against HIV-1.