(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 | 1253049-29-4

• 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: (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
• 英文别名: 4-acetylamino-3-[4-(estra-1,3,5(10)-triene-3,17-dihydroxy-17α-yl)-[1,2,3]triazol-1-yl]-5-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid；(3S,4R,5R)-4-acetamido-3-(4-((8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-5-(pentan-3-yloxy)cyclohex-1-enecarboxylic acid；(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-carboxylic acid
• CAS: 1253049-29-4
• 化学式: C₃₄H₄₆N₄O₆
• 分子量: 606.762
• InChiKey: KXJWRUZGKKGEGN-WGVFSBICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  L-精氨酸 、 (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 以 甲醇 为溶剂， 反应 4.0h， 生成 4-acetylamino-3-[4-(estra-1,3,5(10)-triene-3,17-dihydroxy-17α-yl)-[1,2,3]triazol-1-yl]-5-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid L-arginine salt
  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-[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

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.
• [EN] COMPOUNDS AND METHODS FOR TREATMENT OF INFLUENZA<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT DU VIRUS INFLUENZA
  申请人：UNIV FRASER SIMON

  公开号：WO2010075636A1

  公开（公告）日：2010-07-08

  The present invention provides in part a compound of Formula (I) or a pharmaceutically- acceptable salt or stereoisomer thereof: where R1 is selected from the group consisting of a substituted triazole group, a guanidine group, a urea group, a thiourea group, an amidine group, and N3; and R2 is selected from the group consisting of H, Me, Et and an amino acid, and methods and uses thereof.

  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。