5-acetylamino-6-[2,3-dihydroxy-1-(3-hydroxypropylcarbamoyloxy)propyl]-4-guanidino-5,6-dihydro-4H-pyran-2-carboxylic acid | 1397716-32-3

• 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: 5-acetylamino-6-[2,3-dihydroxy-1-(3-hydroxypropylcarbamoyloxy)propyl]-4-guanidino-5,6-dihydro-4H-pyran-2-carboxylic acid
• 英文别名: (2R,3R,4S)-3-acetamido-4-(diaminomethylideneamino)-2-[(1R,2R)-2,3-dihydroxy-1-(3-hydroxypropylcarbamoyloxy)propyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
• CAS: 1397716-32-3
• 化学式: C₁₆H₂₇N₅O₉
• 分子量: 433.418
• InChiKey: NMMAQWPDYCTUBB-IINAIABHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  239
• 氢给体数：
  8
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  5-acetylamino-6-(2,2-dimethyl-[1,3]dioxolan-4-yl)-3-[(hydroxypropyl)carbamoyloxy]methyl-4-[2,3-bis(tert-butoxycarbonyl)guanidino]-5,6-dihydro-4H-pyran-2-carboxylic acid ethylester 在 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 以84%的产率得到5-acetylamino-6-[2,3-dihydroxy-1-(3-hydroxypropylcarbamoyloxy)propyl]-4-guanidino-5,6-dihydro-4H-pyran-2-carboxylic acid
  参考文献：
  名称：

  ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY

  摘要：

  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。

  公开号：

  US20130274229A1

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。
• Enhanced Anti-influenza Agents Conjugated with Anti-inflammatory Activity
  作者：Kung-Cheng Liu、Jim-Min Fang、Jia-Tsrong Jan、Ting-Jen R. Cheng、Shi-Yun Wang、Shi-Ting Yang、Yih-Shyun E. Cheng、Chi-Huey Wong

  DOI：10.1021/jm3009844

  日期：2012.10.11

  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.