methyl (3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxycyclohexyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylate | 1234466-36-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: methyl (3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxycyclohexyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylate
• 英文别名: methyl (3S,4R,5R)-4-acetamido-3-[4-(1-hydroxycyclohexyl)triazol-1-yl]-5-pentan-3-yloxycyclohexene-1-carboxylate
• CAS: 1234466-36-4
• 化学式: C₂₃H₃₆N₄O₅
• 分子量: 448.563
• InChiKey: PSLWRTFMINDBOE-QKNQBKEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxycyclohexyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylate 在 三甲基氢氧化锡 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.0h， 以61%的产率得到(3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxycyclohexyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylic acid
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS FOR TREATMENT OF INFLUENZA
  [FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT DU VIRUS INFLUENZA

  摘要：

  本发明部分提供了一种化合物，其化学式为（I）或其药用盐或立体异构体：其中R1选自以下组：取代三唑基团、胍基团、脲基团、硫脲基团、酰胺基团和N3；R2选自以下组：H、Me、Et和氨基酸，以及其方法和用途。

  公开号：

  WO2010075636A1
• 作为产物：
  描述：

  methyl (3S,4R,5R)-4-acetamido-3-azido-5-(1-ethylpropoxy)-cyclohex-1-ene-1-carboxylate 、 炔环己醇 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 2.0h， 以85%的产率得到methyl (3S,4R,5R)-4-acetamido-5-(1-ethylpropoxy)-3-[4-(1-hydroxycyclohexyl)[1,2,3]triazol-1-yl]cyclohex-1-ene-1-carboxylate
  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