tylophorine | 1241383-74-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: tylophorine
• 英文别名: tylophorine N-oxide；2,3,6,7-Tetramethoxy-10-oxido-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizin-10-ium
• CAS: 1241383-74-3
• 化学式: C₂₄H₂₇NO₅
• 分子量: 409.482
• InChiKey: JJGAPUUIERNMBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3,6,7-Tetramethoxy-9,10,11,12,12a,13-hexahydro-9a-aza-cyclopenta[b]triphenylene 在 双氧水 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以80.1%的产率得到tylophorine
  参考文献：
  名称：

  Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus

  摘要：

  The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC50) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS Coy), with EC50 values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS Coy infection. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2010.08.009

文献信息

• PHENANTHROINDOLIZIDINE ANALOGUES
  申请人：Lee Shiow-Ju

  公开号：US20100216773A1

  公开（公告）日：2010-08-26

  Treatment of coronavirus infection with phenanthroindolizidine analogues.

  使用菲南三氮杂环吲哚啉类似物治疗冠状病毒感染。
• US8440649B2
  申请人：——

  公开号：US8440649B2

  公开（公告）日：2013-05-14
• Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus
  作者：Cheng-Wei Yang、Yue-Zhi Lee、Iou-Jiun Kang、Dale L. Barnard、Jia-Tsrong Jan、Du Lin、Chun-Wei Huang、Teng-Kuang Yeh、Yu-Sheng Chao、Shiow-Ju Lee

  DOI：10.1016/j.antiviral.2010.08.009

  日期：2010.11

  The discovery and development of new, highly potent anti-coronavirus agents and effective approaches for controlling the potential emergence of epidemic coronaviruses still remains an important mission. Here, we identified tylophorine compounds, including naturally occurring and synthetic phenanthroindolizidines and phenanthroquinolizidines, as potent in vitro inhibitors of enteropathogenic coronavirus transmissible gastroenteritis virus (TGEV). The potent compounds showed 50% maximal effective concentration (EC50) values ranging from 8 to 1468 nM as determined by immunofluorescent assay of the expression of TGEV N and S proteins and by real time-quantitative PCR analysis of viral yields. Furthermore, the potent tylophorine compounds exerted profound anti-TGEV replication activity and thereby blocked the TGEV-induced apoptosis and subsequent cytopathic effect in ST cells. Analysis of the structure-activity relations indicated that the most active tylophorine analogues were compounds with a hydroxyl group at the C14 position of the indolizidine moiety or at the C3 position of the phenanthrene moiety and that the quinolizidine counterparts were more potent than indolizidines. In addition, tylophorine compounds strongly reduced cytopathic effect in Vero 76 cells induced by human severe acute respiratory syndrome coronavirus (SARS Coy), with EC50 values ranging from less than 5 to 340 nM. Moreover, a pharmacokinetic study demonstrated high and comparable oral bioavailabilities of 7-methoxycryptopleurine (52.7%) and the naturally occurring tylophorine (65.7%) in rats. Thus, our results suggest that tylophorine compounds are novel and potent anti-coronavirus agents that may be developed into therapeutic agents for treating TGEV or SARS Coy infection. (C) 2010 Elsevier B.V. All rights reserved.