3-[[(2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carbonyl]amino]propanoic acid | 1421960-33-9

• 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: 3-[[(2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carbonyl]amino]propanoic acid
• CAS: 1421960-33-9
• 化学式: C₁₅H₂₅N₅O₈
• 分子量: 403.392
• InChiKey: MPVYHCYTLXNCOU-RFCPQYNYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  230
• 氢给体数：
  8
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-[[(2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carbonyl]amino]propanoic acid 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-((2R,3R,4S)-3-acetamido-4-guanidino-2-((1R,2R)-1,2,3-trihydroxypropyl)-3,4-dihydro-2H-pyran-6-carboxamido)propanoic acid 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：

  N-acetyl neuraminic acid 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 、 caesium carbonate 、 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 、 sodium hydroxide 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 苯 为溶剂， 反应 137.67h， 生成 3-[[(2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carbonyl]amino]propanoic 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

文献信息

• Structure-Based Design and Synthesis of C-1- and C-4-Modified Analogs of Zanamivir as Neuraminidase Inhibitors
  作者：Enguang Feng、Woo-Jin Shin、Xuelian Zhu、Jian Li、Deju Ye、Jiang Wang、Mingyue Zheng、Jian-Ping Zuo、Kyoung Tai No、Xian Liu、Weiliang Zhu、Wei Tang、Baik-Lin Seong、Hualiang Jiang、Hong Liu

  DOI：10.1021/jm3009713

  日期：2013.2.14

  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.