(4S,5R,6R)-5-(acetylamino)-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-6-((1R,2R),3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid benzhydryl ester | 185382-06-3

• 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: (4S,5R,6R)-5-(acetylamino)-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-6-((1R,2R),3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid benzhydryl ester
• 英文别名: Benzhydryl (2R,3R,4S)-3-(acetylamino)-4-({(E)-[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl}amino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate；benzhydryl (2R,3R,4S)-3-acetamido-4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 185382-06-3
• 化学式: C₃₅H₄₆N₄O₁₁
• 分子量: 698.77
• InChiKey: UQZBEMJIUHIGPS-BUVDNBABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  50
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  214
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (4S,5R,6R)-5-(acetylamino)-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-6-((1R,2R),3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid benzhydryl ester 在 吡啶 、 sodium chlorite 、 sodium periodate 、 potassium dihydrogenphosphate 、 环己烯 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 10.5h， 生成 benzhydryl (2R,3R,4S)-3-acetamido-4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-2-(diethylcarbamoyl)-3,4-dihydro-2H-pyran-6-carboxylate
  参考文献：
  名称：

  Smith, Paul W.; Sollis, Steven L.; Howes, Peter D., Journal of Medicinal Chemistry, 1998, vol. 41, # 6, p. 787 - 797

  摘要：

  DOI：
• 作为产物：
  描述：

  扎那米韦中间体2 在 盐酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 (4S,5R,6R)-5-(acetylamino)-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-6-((1R,2R),3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  Smith, Paul W.; Sollis, Steven L.; Howes, Peter D., Journal of Medicinal Chemistry, 1998, vol. 41, # 6, p. 787 - 797

  摘要：

  DOI：

文献信息

• Potent and Long-Acting Dimeric Inhibitors of Influenza Virus Neuraminidase Are Effective at a Once-Weekly Dosing Regimen
  作者：Simon J. F. Macdonald、Keith G. Watson、Rachel Cameron、David K. Chalmers、Derek A. Demaine、Rob J. Fenton、David Gower、J. Nicole Hamblin、Stephanie Hamilton、Graham J. Hart、Graham G. A. Inglis、Betty Jin、Haydn T. Jones、Darryl B. McConnell、Andy M. Mason、Van Nguyen、Ian J. Owens、Nigel Parry、Phillip A. Reece、Stephen E. Shanahan、Donna Smith、Wen-Yang Wu、Simon P. Tucker

  DOI：10.1128/aac.48.12.4542-4549.2004

  日期：2004.12

  Dimeric derivatives (compounds 7 to 9) of the influenza virus neuraminidase inhibitor zanamivir (compound 2), which have linking groups of 14 to 18 atoms in length, are approximately 100-fold more potent inhibitors of influenza virus replication in vitro and in vivo than zanamivir. The observed optimum linker length of 18 to 22 Å, together with observations that the dimers cause aggregation of isolated neuraminidase tetramers and whole virus, indicate that the dimers benefit from multivalent binding via intertetramer and intervirion linkages. The outstanding long-lasting protective activities shown by compounds 8 and 9 in mouse influenza infectivity experiments and the extremely long residence times observed in the lungs of rats suggest that a single low dose of a dimer would provide effective treatment and prophylaxis for influenza virus infections.

  摘要 流感病毒神经氨酸酶抑制剂扎那米韦（化合物 2）的二聚体衍生物（化合物 7 至 9）具有长度为 14 至 18 个原子的连接基团，在体外和体内对流感病毒复制的抑制作用比扎那米韦强约 100 倍。所观察到的 18 至 22 Å 的最佳连接长度，以及二聚体会导致分离的神经氨酸酶四聚体和整个病毒聚集的观察结果，都表明二聚体通过四聚体间和病毒间的连接而受益于多价结合。化合物 8 和 9 在小鼠流感感染性实验中表现出的出色的持久保护活性，以及在大鼠肺部观察到的极长的停留时间都表明，二聚体的单次低剂量使用将为流感病毒感染提供有效的治疗和预防。
• Intermediates for preparing neuraminidase inhibitor conjugates
  申请人：Biota Scientific Management Pty Ltd

  公开号：US07230114B2

  公开（公告）日：2007-06-12

  Compounds of formula (I), methods for their preparation and their use in the manufacture of neuraminidase inhibitor conjugates. Wherein R represents as carboxylic acid protecting group; P1 and P2 can be the same or different and are selected from amine protecting groups; P3 represents a protecting group for 1, 2 diols; and LG represents a leaving group

  式(I)的化合物，其制备方法以及它们在制造神经氨酸酶抑制剂共轭物中的用途。其中R代表羧酸保护基；P1和P2可以相同也可以不同，并且是从胺保护基中选择的；P3代表1,2-二醇的保护基；LG代表离去基。
• 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。
• 6-CARBOXAMIDO DIHYDROPYRAN DERIVATIVES
  申请人：BIOTA SCIENTIFIC MANAGEMENT PTY. LTD.

  公开号：EP0833825B1

  公开（公告）日：2001-09-26
• Smith, Paul W.; Sollis, Steven L.; Howes, Peter D., Journal of Medicinal Chemistry, 1998, vol. 41, # 6, p. 787 - 797
  作者：Smith, Paul W.、Sollis, Steven L.、Howes, Peter D.、Cherry, Peter C.、Starkey, Lan D.、Cobley, Kevin N.、Weston, Helen、Scicinski, Jan、Merritt, Andrew、Whittington, Andrew、Wyatt, Paul、Taylor, Neil、Green, Darren、Bethell, Richard、Madar, Safia、Fenton, Robert J.、Morley, Peter J.、Pateman, Tony、Beresford, Alan

  DOI：——

  日期：——