methyl (3S,4R,5R)-4-acetamido-3-[4-(3,17-dihydroxy-estra-1,3,5(10)-trien-17α-yl)[1,2,3]triazol-1-yl]-5-(1-ethylpropoxy)-cyclohex-1-ene-1-carboxylate | 1253049-30-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: methyl (3S,4R,5R)-4-acetamido-3-[4-(3,17-dihydroxy-estra-1,3,5(10)-trien-17α-yl)[1,2,3]triazol-1-yl]-5-(1-ethylpropoxy)-cyclohex-1-ene-1-carboxylate
• 英文别名: methyl (3S,4R,5R)-4-acetamido-3-[4-[(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]triazol-1-yl]-5-pentan-3-yloxycyclohexene-1-carboxylate
• CAS: 1253049-30-7
• 化学式: C₃₅H₄₈N₄O₆
• 分子量: 620.789
• InChiKey: ITUGSZZNCWRPPT-XCYVMIMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (3S,4R,5R)-4-acetamido-3-[4-(3,17-dihydroxy-estra-1,3,5(10)-trien-17α-yl)[1,2,3]triazol-1-yl]-5-(1-ethylpropoxy)-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72%的产率得到(3S,4R,5R)-4-acetamido-3-[4-(3,17-dihydroxy-estra-1,3,5(10)-triene-17α-yl)[1,2,3]triazol-1-yl]-5-(1-ethylpropoxy)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
• 作为产物：
  描述：

  methyl (3S,4R,5R)-4-acetamido-3-azido-5-(1-ethylpropoxy)-cyclohex-1-ene-1-carboxylate 、 炔雌醇 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 2.0h， 以76%的产率得到methyl (3S,4R,5R)-4-acetamido-3-[4-(3,17-dihydroxy-estra-1,3,5(10)-trien-17α-yl)[1,2,3]triazol-1-yl]-5-(1-ethylpropoxy)-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