5-(4-methylpiperazinyl)-6-chloro-2-pyrazinecarboxylic acid | 150331-98-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-(4-methylpiperazinyl)-6-chloro-2-pyrazinecarboxylic acid
• 英文别名: 6-Chloro-5-(4-methyl-1-piperazinyl)-2-pyrazinecarboxylic acid；6-chloro-5-(4-methylpiperazin-1-yl)pyrazine-2-carboxylic acid
• CAS: 150331-98-9
• 化学式: C₁₀H₁₃ClN₄O₂
• 分子量: 256.692
• InChiKey: CAGNNBFMQUXZKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 3-amino-5-(4-methylpiperazinyl)-6-chloro-2-pyrazinoate 在 palladium on activated charcoal sodium hydroxide 、 氢溴酸 、 氢气 、 溴 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 溶剂黄146 为溶剂， 反应 48.5h， 生成 5-(4-methylpiperazinyl)-6-chloro-2-pyrazinecarboxylic acid
  参考文献：
  名称：

  Potent HIV protease inhibitors: the development of tetrahydrofuranylglycines as novel P2-ligands and pyrazine amides as P3-ligands

  摘要：

  A series of protease inhibitors bearing constrained unnatural amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral activities were evaluated. Replacement of P2-asparagine of compound 1 with (2S,3'R)-tetrahydrofuranylglycine resulted in improvement in enzyme inhibitory as well as antiviral potencies (compound 23). Interestingly, incorporation of (2S,3'S)-tetrahydrofuranylglycine at the P2-position proved to be less effective. The resulting compound 24 was 100-fold less potent than the 2S,3R-isomer (compound 23). This stereochemical preference indicated a hydrogen-bonding interaction between the tetrahydrofuranyl oxygen and the residues of the S2-region of the enzyme active site. Furthermore, replacement of P3-quinolinoyl ligand of 1 with various novel heterocycles resulted in potent inhibitors of HIV proteases. Of particular interest, compound 2 with (2S,3'R)-tetrahydrofuranylglycine at P2 and pyrazine derivative at P3 is one of the most potent inhibitors of HIV-1 (IC50 value 0.07 nM) and HIV-2 (IC50 value 0.18 nM) proteases. Another important result in this series is the identification of compound 27 in which the P2-P3-amide carbonyl has been removed. The resulting compound 27 has exhibited improvement in antiviral potency while retaining the enzyme inhibitory potency similar to compound 1.

  DOI：

  10.1021/jm00068a006