(4R,5R)-4-acetamido-5-pentan-3-yloxy-3-[4-(2-phenylethyl)triazol-1-yl]cyclohex-2-ene-1-carboxylate;(2S)-5-[[amino(azaniumyl)methylidene]amino]-2-azaniumylpentanoate | 1253049-35-2

• 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: (4R,5R)-4-acetamido-5-pentan-3-yloxy-3-[4-(2-phenylethyl)triazol-1-yl]cyclohex-2-ene-1-carboxylate;(2S)-5-[[amino(azaniumyl)methylidene]amino]-2-azaniumylpentanoate
• CAS: 1253049-35-2
• 化学式: C₆H₁₄N₄O₂*C₂₄H₃₂N₄O₄
• 分子量: 614.745
• InChiKey: MMZXOCDKKDORLL-AJDAEXCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.54
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  234
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  L-精氨酸 、 (4R,5R)-4-acetamido-5-(pentan-3-yloxy)-3-(4-phenethyl-1H-1,2,3-triazol-1-yl)cyclohex-2-enecarboxylic acid 以 甲醇 为溶剂， 反应 4.0h， 以11.2 mg的产率得到(4R,5R)-4-acetamido-5-pentan-3-yloxy-3-[4-(2-phenylethyl)triazol-1-yl]cyclohex-2-ene-1-carboxylate;(2S)-5-[[amino(azaniumyl)methylidene]amino]-2-azaniumylpentanoate
  参考文献：
  名称：

  Carbocycles Related to Oseltamivir as Influenza Virus Group-1-Specific Neuraminidase Inhibitors. Binding to N1 Enzymes in the Context of Virus-like Particles

  摘要：

  We report here the exploitation of the 150-cavity in the active sites of group-1 neuraminidases for the design of new triazole-containing carbocycles related to oseltamivir. Inhibition studies with virus-like particles (VLPs) containing the influenza virus neuraminidase-1 (NI) activity indicate that several candidates are inhibitors, with K(i) values in the 10(-5)-10(-8) M range. In contrast, a known candidate that preserves the free amino group and a new candidate containing a guanidine function are better inhibitors, with K(i) values of 1.5 x 10(-9) and 4.6 x 10(-10) M, respectively. The most active inhibitor of the N1 enzyme in the triazole series was selective for the N1 class and showed significantly less inhibition (K(i) = 2.6 mu M vs 0.07 mu M) of the free influenza virus neuraminidase-2 (N2). In addition, saturation transfer difference (STD) NMR spectroscopic studies with this compound and the VLPs show that the entire molecule forms contacts with residues in the active site. These data taken together support our proposed binding mode in which the active site and the adjoining 150-cavity are both occupied.

  DOI：

  10.1021/jm100822f

文献信息

• Carbocycles Related to Oseltamivir as Influenza Virus Group-1-Specific Neuraminidase Inhibitors. Binding to N1 Enzymes in the Context of Virus-like Particles
  作者：Sankar Mohan、Sarah McAtamney、Thomas Haselhorst、Mark von Itzstein、Brian Mario Pinto

  DOI：10.1021/jm100822f

  日期：2010.10.28

  We report here the exploitation of the 150-cavity in the active sites of group-1 neuraminidases for the design of new triazole-containing carbocycles related to oseltamivir. Inhibition studies with virus-like particles (VLPs) containing the influenza virus neuraminidase-1 (NI) activity indicate that several candidates are inhibitors, with K(i) values in the 10(-5)-10(-8) M range. In contrast, a known candidate that preserves the free amino group and a new candidate containing a guanidine function are better inhibitors, with K(i) values of 1.5 x 10(-9) and 4.6 x 10(-10) M, respectively. The most active inhibitor of the N1 enzyme in the triazole series was selective for the N1 class and showed significantly less inhibition (K(i) = 2.6 mu M vs 0.07 mu M) of the free influenza virus neuraminidase-2 (N2). In addition, saturation transfer difference (STD) NMR spectroscopic studies with this compound and the VLPs show that the entire molecule forms contacts with residues in the active site. These data taken together support our proposed binding mode in which the active site and the adjoining 150-cavity are both occupied.