5-acetylamino-4-[2,3-bis(tert-butoxycarbonyl)guanidino]-6-[((2,2-dimethyl-[1,3]dioxolan-4-yl)-(4-nitrophenoxy)carbonyloxy)methyl]-5,6-dihydro-4H-pyran-2-carboxylic acid ethyl ester

• 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: 5-acetylamino-4-[2,3-bis(tert-butoxycarbonyl)guanidino]-6-[((2,2-dimethyl-[1,3]dioxolan-4-yl)-(4-nitrophenoxy)carbonyloxy)methyl]-5,6-dihydro-4H-pyran-2-carboxylic acid ethyl ester
• 英文别名: methyl (2R,3R,4S)-3-acetamido-4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-2-[(S)-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-(4-nitrophenoxy)carbonyloxymethyl]-3,4-dihydro-2H-pyran-6-carboxylate
• 化学式: C₃₃H₄₅N₅O₁₅
• 分子量: 751.745
• InChiKey: LICPJPFWGRGQNK-KZQIJMTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  53
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  254
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  5-acetylamino-4-[2,3-bis(tert-butoxycarbonyl)guanidino]-6-[((2,2-dimethyl-[1,3]dioxolan-4-yl)-(4-nitrophenoxy)carbonyloxy)methyl]-5,6-dihydro-4H-pyran-2-carboxylic acid ethyl ester 在 4-二甲氨基吡啶 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 吡啶 、 水 、 叔丁醇 为溶剂， 反应 66.0h， 生成
  参考文献：
  名称：

  Synthesis of C-4 and C-7 triazole analogs of zanamivir as multivalent sialic acid containing scaffolds

  摘要：

  The relative reactivities of C-4 and C-7 azides derived from zanamivir were compared in cycloaddition reactions with a panel of alkynes. All of the reactions proceeded efficiently with no observable differences between primary and secondary azides. Significant rate differences were observed between several members of the alkyne panel. Most notably, a trialkyne derived from a 1,3,5-triazine core underwent complete reaction within 4 h, whereas an analogous trialkyne with an all carbon aromatic core required 18 h. These results suggest that the triazine core serves as an internal catalyst. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2007.06.002
• 作为产物：
  描述：

  methyl 5-acetamido-2,6-anhydro-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid 在 4-二甲氨基吡啶 、 氢气 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 11.0h， 生成 5-acetylamino-4-[2,3-bis(tert-butoxycarbonyl)guanidino]-6-[((2,2-dimethyl-[1,3]dioxolan-4-yl)-(4-nitrophenoxy)carbonyloxy)methyl]-5,6-dihydro-4H-pyran-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  WO2020051498A5

  摘要：

  公开号：

  WO2020051498A5

文献信息

• ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY
  申请人：ACADEMIA SINICA

  公开号：US20130274229A1

  公开（公告）日：2013-10-17

  Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

  新型双靶向、双功能抗流感药物通过与抗炎药物结合形成。根据本发明的示例药物包括咖啡酸（CA）基底的扎那米韦（ZA）共轭物ZA-7-CA（1）、ZA-7-CA酰胺（7）和ZA-7-Nap（43），用于同时抑制流感病毒神经氨基酸酶和抑制促炎细胞因子。提供了用于制备这些增强型抗流感共轭药物的合成方法。合成的双功能ZA共轭物对保护由H1N1或H5N1流感病毒致命感染的小鼠具有协同作用。ZA-7-CA、ZA-7-CA酰胺和ZA-7-Nap共轭物的疗效远远优于ZA与抗炎药物的联合治疗。
• Structure-Based Tetravalent Zanamivir with Potent Inhibitory Activity against Drug-Resistant Influenza Viruses
  作者：Lifeng Fu、Yuhai Bi、Yan Wu、Shanshan Zhang、Jianxun Qi、Yan Li、Xuancheng Lu、Zhenning Zhang、Xun Lv、Jinghua Yan、George F. Gao、Xuebing Li

  DOI：10.1021/acs.jmedchem.6b00537

  日期：2016.7.14

  neuraminidase (NA), but resistant viruses containing mutant NAs with diminished drug affinity are increasingly emerging. Using the structural knowledge of both drug-binding sites and their spatial arrangement on the homotetrameric NA, we have developed a tetravalent zanamivir (TZ) molecule that exhibited marked increases in NA binding affinity, inhibition of NA enzyme activity, and in vitro plus in vivo antiviral

  扎那米韦和奥司他韦是靶向病毒神经氨酸酶（NA）的主要流感抗病毒药物，但是越来越多的人出现了含有突变NA且耐药性降低的抗性病毒。利用两种药物结合位点的结构知识以及它们在同四聚体NA上的空间排列，我们开发了一种四价扎那米韦（TZ）分子，该分子在NA结合亲和力，NA酶活性的抑制以及体外和体内均显着增加。优于扎那米韦的抗病毒功效。TZ可以抵抗人类季节性H3N2和禽类H7N9病毒，包括抗药性突变体。带有TZ的抗性N9 NA的晶体结构说明了该功能，该结果表明四个zanamivir残基同时与NA的所有四个单体结合。本研究中描述的TZ设计方法可能对开发靶向具有多个结合位点的蛋白质的药物或配体有用。TZ的强力抗流感活性使其对进一步开发具有吸引力。
• ZANAMIVIR PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY AND DETERMINING OSELTAMIVIR SUSCEPTIBILITY OF INFLUENZA VIRUSES
  申请人：Wong Chi-Huey

  公开号：US20130225532A1

  公开（公告）日：2013-08-29

  Methods and compositions for detection of drug resistant pathogens and treatment against infections thereof are provided. Methods for detection of oseltamivir-resistant influenza viruses by competitive binding assays utilizing non-oseltamivir influenza virus neuraminidase inhibitors and oseltamivir carboxylate are provided. Influenza virus neuraminidase inhibitors coupled to sensors and useful for employment in the methods of the invention are disclosed. Novel phosphonate compounds active as neuraminidase inhibitors against wild-type and oseltamivir-resistant influenza strains of H1N1, H5N1 and H3N2 viruses are disclosed. An enantioselective synthetic route to preparation of these phosphonate compounds via sialic acid is provided.

  本发明提供了检测耐药病原体和治疗感染的方法和组合物。本发明提供了利用非奥司他韦流感病毒神经氨酸酶抑制剂和奥司他韦羧酸盐进行竞争结合测定的检测奥司他韦耐药性流感病毒的方法。本发明还揭示了与传感器耦合并在本发明方法中使用的流感病毒神经氨酸酶抑制剂。本发明还揭示了对H1N1、H5N1和H3N2病毒的野生型和奥司他韦耐药株具有神经氨酸酶抑制剂活性的新型膦酸酯化合物。本发明还提供了通过唾液酸的对映选择性合成途径制备这些膦酸酯化合物的方法。
• Synergistic Effect of Zanamivir−Porphyrin Conjugates on Inhibition of Neuraminidase and Inactivation of Influenza Virus
  作者：Wen-Hsien Wen、Mengi Lin、Ching-Yao Su、Shi-Yun Wang、Yih-Shyun E. Cheng、Jim-Min Fang、Chi-Huey Wong

  DOI：10.1021/jm900515g

  日期：2009.8.13

  New anti-influenza agents of tetravalent zanamivir on a porphyrin scaffold were synthesized. These compounds are 10 to 100 times more potent in inhibiting influenza replications even though they are somewhat less potent in neuraminidase inhibition than the monomeric zanamivir. The enhanced anti-influenza activity is probably attributable to the additional viral inactivation by singlet oxygen due to sensitization of the porphyrin moiety, which is brought in close proximity of virus by the conjugated zanamivir in a manner resembling the "magic bullet" mechanism.
• ZANAMIVIR PHOSPHONATE CONGENERS WITH ANTI-INFLUENZA ACTIVITY AND DETERMINING OSELTAMIVIR SUSCEPTIBILITY OF INFLUENZA VIRUSES
  申请人：Academia Sinica

  公开号：EP2568976B1

  公开（公告）日：2015-09-30