(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1-[[4-[4-[[[(1R,2R)-1-[(2R,3R,4S)-3-acetamido-6-carboxy-4-guanidino-3,4-dihydro-2H-pyran-2-yl]-2,3-dihydroxy-propoxy]carbonylamino]methyl]phenyl]phenyl]methylcarbamoyloxy]-2,3-dihydroxy-propyl]-4-guanidino-3,4-dihydro-2H-pyran-6-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R,3R,4S)-3-acetamido-2-[(1R,2R)-1-[[4-[4-[[[(1R,2R)-1-[(2R,3R,4S)-3-acetamido-6-carboxy-4-guanidino-3,4-dihydro-2H-pyran-2-yl]-2,3-dihydroxy-propoxy]carbonylamino]methyl]phenyl]phenyl]methylcarbamoyloxy]-2,3-dihydroxy-propyl]-4-guanidino-3,4-dihydro-2H-pyran-6-carboxylic acid
• 英文别名: (2R,3R,4S)-3-acetamido-2-[(1R,2R)-1-[[4-[4-[[[(1R,2R)-1-[(2R,3R,4S)-3-acetamido-6-carboxy-4-(diaminomethylideneamino)-3,4-dihydro-2H-pyran-2-yl]-2,3-dihydroxypropoxy]carbonylamino]methyl]phenyl]phenyl]methylcarbamoyloxy]-2,3-dihydroxypropyl]-4-(diaminomethylideneamino)-3,4-dihydro-2H-pyran-6-carboxylic acid
• 化学式: C₄₀H₅₂N₁₀O₁₆
• 分子量: 928.91
• InChiKey: RVODFFKWWDBAIQ-JMMOPUKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  66
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  438
• 氢给体数：
  14
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以57%的产率得到(2R,3R,4S)-3-acetamido-2-[(1R,2R)-1-[[4-[4-[[[(1R,2R)-1-[(2R,3R,4S)-3-acetamido-6-carboxy-4-guanidino-3,4-dihydro-2H-pyran-2-yl]-2,3-dihydroxy-propoxy]carbonylamino]methyl]phenyl]phenyl]methylcarbamoyloxy]-2,3-dihydroxy-propyl]-4-guanidino-3,4-dihydro-2H-pyran-6-carboxylic acid
  参考文献：
  名称：

  Dimeric Zanamivir Conjugates with Various Linking Groups Are Potent, Long-Lasting Inhibitors of Influenza Neuraminidase Including H5N1 Avian Influenza

  摘要：

  The synthesis, antiviral and pharmacokinetic properties of zanamivir (ZMV) dimers 8 and 13 are described. The compounds are highly potent neuraminidase (NA) inhibitors which, along with dimer 3, are being investigated as potential second generation inhaled therapies both for the treatment of influenza and for prophylactic use. They show outstanding activity in a 1 week mouse influenza prophylaxis assay, and compared with ZMV, high concentrations of 8 and 13 are found in rat lung tissue after 1 week. Retention of compounds in rat lung tissue correlated both with molecular weight (excluding 3 and 15) and with a capacity factor K derived from immobilized artificial membrane (IAM) chromatography (including 3 and 15). Pharmacokinetic parameters for 3, 8 and 13 in rats show the compounds have short to moderate plasma half-lives, low clearances and low volumes of distribution. Dimer 3 shows NA inhibitory activity against N1 viruses including the recent highly pathogenic H5N1 A/Chicken/Vietnam/8/2004. In plaque reduction assays, 3, 8 and 13 show good to outstanding potency against a panel of nine flu A and B virus strains. Consistent with its shorter and more rigid linking group, dimer 8 has been successfully crystallized.

  DOI：

  10.1021/jm040891b

文献信息

• Dimeric compounds and their use as anti-viral agents
  申请人：Demaine A. Derek

  公开号：US20050054718A1

  公开（公告）日：2005-03-10

  The invention relates to compounds of general formula (I), in which: R is an amino or guanidino group; R 2 is acetyl or trifluoroacetyl; n and q are either the same or different and selected from 0, 1 or 2; and X is an optionally substituted phenyl, optionally substituted naphthyl or optionally substituted phenyl-Y-optionally substituted phenyl in which Y is selected from a covalent bond, CH 2 , CH 2 CH 2 , O or SO 2 , or a pharmaceutically acceptable derivative thereof, with the proviso that when X is phenyl or naphthyl, n and q are both 2 and when X is phenyl-Y-phenyl in which Y is a covalent bond, then n and q are not both 0, methods for their preparation, pharmaceutical formulations containing them or their use in the prevention or treatment of a viral infection.

  本发明涉及通式(I)的化合物，其中：R 是氨基或胍基； R 2 是乙酰基或三氟乙酰基；n 和 q 可以相同或不同，选自 0、1 或 2；X 是任选取代的苯基、任选取代的萘基或任选取代的苯基-Y-任选取代的苯基，其中 Y 选自共价键、CH 2 、CH 2 CH 2 2 O 或 SO 2 或其药学上可接受的衍生物，但当 X 为苯基或萘基时，n 和 q 均为 2；当 X 为苯基-Y-苯基（其中 Y 为共价键）时，则 n 和 q 均不为 0。
• DIMERIC COMPOUNDS AND THEIR USE AS ANTI-VIRAL AGENTS
  申请人：Demaine A. Derek

  公开号：US20070225361A1

  公开（公告）日：2007-09-27

  The invention relates to compounds of general formula (I), in which: R is an amino or guanidino group; R 2 is acetyl or trifluoroacetyl; n and q are either the same or different and selected from 0, 1 or 2; and X is an optionally substituted phenyl, optionally substituted naphthyl or optionally substituted phenyl-Y-optionally substituted phenyl in which Y is selected from a covalent bond, CH 2 , CH 2 CH 2 , O or SO 2 , or a pharmaceutically acceptable derivative thereof, with the proviso that when X is phenyl or naphthyl, n and q are both 2 and when X is phenyl-Y-phenyl in which Y is a covalent bond, then n and q are not both 0, methods for their preparation, pharmaceutical formulations containing them or their use in the prevention or treatment of a viral infection.
• US7214707B2
  申请人：——

  公开号：US7214707B2

  公开（公告）日：2007-05-08
• US7504434B2
  申请人：——

  公开号：US7504434B2

  公开（公告）日：2009-03-17