ethyl 4-acetamido-3-[2,3-bis(tert-butoxycarbonyl)guanidino]-5-(1,2,3-triacetoxy)propyl-(6-oxacyclohex-1-ene)carboxylate | 1333324-36-9

• 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: ethyl 4-acetamido-3-[2,3-bis(tert-butoxycarbonyl)guanidino]-5-(1,2,3-triacetoxy)propyl-(6-oxacyclohex-1-ene)carboxylate
• 英文别名: ethyl {(4S,5R,6R)-5-acetamido-4-[2,3-bis(tert-butoxycarbonyl)guanidino]-6-[(1S,2R)-1,2,3-triacetoxy]-propyl-4,5,6-trihydropyran-2-yl}carboxylate；ethyl (2R,3R,4S)-3-acetamido-4-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]-2-[(1S,2R)-1,2,3-triacetyloxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 1333324-36-9
• 化学式: C₃₀H₄₆N₄O₁₄
• 分子量: 686.714
• InChiKey: DEGOGDCLQHGZLO-JGSPDANKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  48
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  233
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  ethyl 4-acetamido-3-[2,3-bis(tert-butoxycarbonyl)guanidino]-5-(1,2,3-triacetoxy)propyl-(6-oxacyclohex-1-ene)carboxylate 在 吗啉 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 sodium ethanolate 、 potassium carbonate 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 38.0h， 生成
  参考文献：
  名称：

  Enhanced Anti-influenza Agents Conjugated with Anti-inflammatory Activity

  摘要：

  Influenza therapy with a single targeted compound is often limited in efficacy due to the rapidly developed drug resistance. Moreover, the uncontrolled virus-induced cytokines could cause the high mortality of human infected by H5N1 avian influenza virus. In this study, we explored the novel dual-targeted bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents. In particular, the caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1) and ZA-7-CA-amide (7) showed simultaneous inhibition of influenza virus neuraminidase and suppression of pro-inflammatory cytokines. These ZA conjugates provided remarkable protection of cells and mice against influenza infections. Intranasal administration of low dosage (<1.2 mu mol/kg/day) of ZA conjugates exhibited much greater effect than the combination therapy with ZA and the anti-inflammatory agents in protection of the lethally infected mice by H1N1 or H5N1 influenza viruses.

  DOI：

  10.1021/jm3009844
• 作为产物：
  描述：

  ethyl 4-acetamido-1-acetoxy-3-nitro-5-(1,2,3-triacetoxy)propyl-(6-oxacyclohexane)carboxylate 在 三氟甲磺酸三甲基硅酯 、 溶剂黄146 、 三乙胺 、 mercury dichloride 、 锌 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 18.5h， 生成 ethyl 4-acetamido-3-[2,3-bis(tert-butoxycarbonyl)guanidino]-5-(1,2,3-triacetoxy)propyl-(6-oxacyclohex-1-ene)carboxylate
  参考文献：
  名称：

  通过不对称的Aza-Henry反应全合成抗流感药Zanamivir和Zanaphosphor

  摘要：

  有效的抗流感药物扎那米韦及其膦酸酯同类物，是通过使用硝基作为C4上的潜在氨基，与手性亚磺胺碱进行不对称aza-Henry反应而合成的，手性亚磺胺碱衍生自廉价的d-葡萄糖酸-δ-内酯在C5建立必需的含氮取代基。该方法提供了构建扎那米韦和扎那磷的密集取代的二氢吡喃核芯的有效方法，而无需使用危险的叠氮化物试剂。

  DOI：

  10.1021/acs.orglett.6b02131

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。
• Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir
  作者：Kung-Cheng Liu、Pei-Shan Lee、Shi-Yun Wang、Yih-Shyun E. Cheng、Jim-Min Fang、Chi-Huey Wong

  DOI：10.1016/j.bmc.2011.06.080

  日期：2011.8

  Zanamivir (ZA) is a potent anti-influenza drug, but it cannot be administrated orally because of the hydrophilic carboxylate and guanidinium groups. Guanidino-oseltamivir (GO) is another effective neuraminidase inhibitor with polar guanidinium group under physiological conditions. The ester prodrugs ZA-HNAP (5) and GO-HNAP (6) were prepared to incorporate a 1-hydroxy-2-naphthoic (HNAP) moiety to attain good lipophilicity in the intramolecular ion-pairing forms. ZA-HNAP resumed high anti-influenza activity (EC(50) = 48 nM), in cell-based anti-influenza assays, by releasing zanamivir along with nontoxic HNAP. Under similar conditions, the hydrolysis of the GO-HNAP ester was too sluggish to show the desired anti-influenza activity. (C) 2011 Elsevier Ltd. All rights reserved.
• Dichotomous Selectivity in Indium-Mediated Aza-Barbier-Type Allylation of 2-<i>N</i>-Acetyl Glycosyl Sulfinylimines in Brine: Convenient Access to Potent Anti-Influenza Agents
  作者：Long-Zhi Lin、Sheng Yang、Wan-Hsuan Liu、Jiun-Jie Shie

  DOI：10.1021/acs.joc.1c02121

  日期：2022.3.4