(1R,9S,10S)-15-methoxy-20-methyl-5-[2-(trifluoromethyl)phenyl]-4,6,20-triazapentacyclo[8.7.3.01,9.03,7.012,17]icosa-3(7),5,12(17),13,15-pentaen-16-ol | 902137-61-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (1R,9S,10S)-15-methoxy-20-methyl-5-[2-(trifluoromethyl)phenyl]-4,6,20-triazapentacyclo[8.7.3.01,9.03,7.012,17]icosa-3(7),5,12(17),13,15-pentaen-16-ol
• CAS: 902137-61-5
• 化学式: C₂₆H₂₆F₃N₃O₂
• 分子量: 469.507
• InChiKey: HZXROLRLVLSLJR-HUJREVKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  邻三氟甲基苯甲醛 、 Sinomeninon 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 以71%的产率得到(1R,9S,10S)-15-methoxy-20-methyl-5-[2-(trifluoromethyl)phenyl]-4,6,20-triazapentacyclo[8.7.3.01,9.03,7.012,17]icosa-3(7),5,12(17),13,15-pentaen-16-ol
  参考文献：
  名称：

  Sinomenine derivatives with embedment of nitrogen-containing heterocycles exhibiting potent TNF-αinhibitory activity

  摘要：

  本研究探讨了含有小型药物类氮杂环基团的盐酸缬草碱衍生物对肿瘤坏死因子-α（TNF-α）产生的抑制作用。发现几种具有氯苯基取代基的新型盐酸缬草碱衍生物展现出比天然盐酸缬草碱及其他衍生物更强的TNF-α抑制活性。

  DOI：

  10.1007/s11426-012-4588-8

文献信息

• Modification of poorly bioactive sinomenine into more potent immunosuppressive agents by embedding of drug-like fragments
  作者：Yang-Tong Lou、Hai-Bin Zhou、Jia Zou、Ling-Chen Yan、En-Guan Bi、Bing Sun、Zhu-Jun Yao

  DOI：10.1016/j.tetlet.2009.11.019

  日期：2010.1

  Embedment of drug-like heterocyclic moieties was Successfully employed in the novel modification of the readily available but poorly bioactive natural alkaloid sinomenine. Application of the newly proposed approach afforded a number of more potent sinomenine-like molecules with a significantly high hit rate. Among these new analogous, up to 500-fold increase of in vitro immunosuppressive activity was achieved. Further biological experiments of representative compound 4b indicated that it might inhibit NF-kappa B activation induced by TNF-alpha in a dose dependent way and showed remarkable in vivo treatment effects against the mouse experimental autoimmune uveoretinitis (EAU) disease models. (C) 2009 Elsevier Ltd. All rights reserved.
• Sinomenine derivatives with embedment of nitrogen-containing heterocycles exhibiting potent TNF-αinhibitory activity
  作者：Meng Wang、LiYan Ma、YangTong Lou、Chao Bian、TingTing Zhou、HaiBin Zhou、HongZe Liao、Zhao Ma、DongSheng Yin、AiZhong Chen、ShaoZhong Wang、ZhenYu Yang、Bing Sun、ZhuJun Yao

  DOI：10.1007/s11426-012-4588-8

  日期：2012.12

  Inhibitory effect on tumor necrosis factor-α (TNF-α) production by sinomenine derivatives with embedment of small drug-like nitrogen hetereocyclic moieties has been studied in this work. Several new sinomenine derivatives having chlorophenyl substituent have been found to exhibit much more potent TNF-α inhibitory activity than natural sinomenine and other derivatives.

  本研究探讨了含有小型药物类氮杂环基团的盐酸缬草碱衍生物对肿瘤坏死因子-α（TNF-α）产生的抑制作用。发现几种具有氯苯基取代基的新型盐酸缬草碱衍生物展现出比天然盐酸缬草碱及其他衍生物更强的TNF-α抑制活性。