(3R,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxy-1-methylethyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylic acid | 1253049-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (3R,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxy-1-methylethyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylic acid
• 英文别名: (3R,4R,5R)-4-acetamido-3-[4-(2-hydroxypropan-2-yl)triazol-1-yl]-5-pentan-3-yloxycyclohexene-1-carboxylic acid
• CAS: 1253049-31-8
• 化学式: C₁₉H₃₀N₄O₅
• 分子量: 394.471
• InChiKey: SHZLGTIBAVWRQZ-BFYDXBDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl (3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxy-1-methylethyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以40%的产率得到(3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxy-1-methylethyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylic acid
  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

• COMPOUNDS AND METHODS FOR TREATMENT OF INFLUENZA
  申请人：Pinto Brian Mario

  公开号：US20120010254A1

  公开（公告）日：2012-01-12

  The present invention provides in part a compound of Formula (I) or a pharmaceutically-acceptable salt or stereoisomer thereof: where R 1 is selected from the group consisting of a substituted triazole group, a guanidine group, a urea group, a thiourea group, an amidine group, and N 3 ; and R 2 is selected from the group consisting of H, Me, Et and an amino acid, and methods and uses thereof.
• 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.