(1S,2R)-1-((2R,3R,4S)-3-acetamido-4-(2,3-bis(tertbutoxycarbonyl)guanidino)-6-(3-chlorobenzylcarbamoyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate | 1421960-28-2

• 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: (1S,2R)-1-((2R,3R,4S)-3-acetamido-4-(2,3-bis(tertbutoxycarbonyl)guanidino)-6-(3-chlorobenzylcarbamoyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate
• 英文别名: [(2R,3S)-3-[(2R,3R,4S)-3-acetamido-4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-6-[(3-chlorophenyl)methylcarbamoyl]-3,4-dihydro-2H-pyran-2-yl]-2,3-diacetyloxypropyl] acetate
• CAS: 1421960-28-2
• 化学式: C₃₅H₄₈ClN₅O₁₃
• 分子量: 782.245
• InChiKey: ZQCCMJWYKFBWSK-RXINHCNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  54
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  235
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (1S,2R)-1-((2R,3R,4S)-3-acetamido-4-(2,3-bis(tertbutoxycarbonyl)guanidino)-6-(3-chlorobenzylcarbamoyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 (2R,3R,4S)-3-acetamido-4-guanidino-N-(3-chlorobenzyl)-2-((1R,2R)-1,2,3-trihydroxypropyl)-3,4-dihydro-2H-pyran-6-carboxamide trifluroacetic acid
  参考文献：
  名称：

  Structure-Based Design and Synthesis of C-1- and C-4-Modified Analogs of Zanamivir as Neuraminidase Inhibitors

  摘要：

  In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound 9f exerts the most potency, with IC50 value of 0.013, 0.001, and 0.09 mu M against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC50 = 0.0014 mu M, H5N1 IC50 = 0.012 mu M, H1N1 IC50 = 0.001 mu M). Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t(1/2)) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents.

  DOI：

  10.1021/jm3009713
• 作为产物：
  描述：

  (2S,4S,5R,6R)-benzyl 5-acetamido-2,4-dihydroxy-6-((1R,2R)-1,2,3-trihydroxypropyl)tetrahydro-2H-pyran-1-carboxylate 在 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 、 叠氮磷酸二苯酯 、 palladium 10% on activated carbon 、 硫化氢 、 氢气 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 苯 为溶剂， 反应 113.67h， 生成 (1S,2R)-1-((2R,3R,4S)-3-acetamido-4-(2,3-bis(tertbutoxycarbonyl)guanidino)-6-(3-chlorobenzylcarbamoyl)-3,4-dihydro-2H-pyran-2-yl)propane-1,2,3-triyl triacetate
  参考文献：
  名称：

  Structure-Based Design and Synthesis of C-1- and C-4-Modified Analogs of Zanamivir as Neuraminidase Inhibitors

  摘要：

  In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound 9f exerts the most potency, with IC50 value of 0.013, 0.001, and 0.09 mu M against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC50 = 0.0014 mu M, H5N1 IC50 = 0.012 mu M, H1N1 IC50 = 0.001 mu M). Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t(1/2)) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents.

  DOI：

  10.1021/jm3009713