(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-N-[[1-[3-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]propyl]triazol-4-yl]methyl]-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide | 1438765-67-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-N-[[1-[3-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]propyl]triazol-4-yl]methyl]-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide
• CAS: 1438765-67-3
• 化学式: C₆₉H₁₀₈N₈O₆
• 分子量: 1145.67
• InChiKey: COLVPLQJWIWAQD-RHJITCMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.9
• 重原子数：
  83
• 可旋转键数：
  10
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  201
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  丙烷,1,3-二叠氮- 、 N-propargyl 3β, 16α-dihydroxyolean-12-en-28-amide 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 以87%的产率得到(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-N-[[1-[3-[4-[[[(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]amino]methyl]triazol-1-yl]propyl]triazol-4-yl]methyl]-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxamide
  参考文献：
  名称：

  三萜衍生物，其制备方法和用途

  摘要：

  本发明涉及一类三萜及其衍生物，其制备方法以及在预防和治疗病毒性肝炎中的用途，尤其是治疗和预防病毒性丙型肝炎。其中所述三萜及其衍生物如说明书所述结构式1和式2的化合物或其药学上可接受的盐或它们的水合物，其中的取代基和符号见说明书定义。

  公开号：

  CN103127135B

文献信息

• 三萜衍生物，其制备方法和用途
  申请人：北京大学

  公开号：CN103127135B

  公开（公告）日：2018-05-04

  本发明涉及一类三萜及其衍生物，其制备方法以及在预防和治疗病毒性肝炎中的用途，尤其是治疗和预防病毒性丙型肝炎。其中所述三萜及其衍生物如说明书所述结构式1和式2的化合物或其药学上可接受的盐或它们的水合物，其中的取代基和符号见说明书定义。
• Development of Oleanane-Type Triterpenes as a New Class of HCV Entry Inhibitors
  作者：Fei Yu、Qi Wang、Zhen Zhang、Yiyun Peng、Yunyan Qiu、Yongying Shi、Yongxiang Zheng、Sulong Xiao、Han Wang、Xiaoxi Huang、Linyi Zhu、Kunbo Chen、Chuanke Zhao、Chuanling Zhang、Maorong Yu、Dian Sun、Lihe Zhang、Demin Zhou

  DOI：10.1021/jm301910a

  日期：2013.6.13

  Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 mu M. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications. Hydroxylation at C-16 significantly enhanced its potency for inhibiting HCV entry with IC50 at 1.4 mu M. Further modification by conjugation of this new lead with a disaccharide at 28-COOH removed the undesired hemolytic effect and, more importantly, increased its potency by similar to 5-fold (54a, IC50 0.3 mu M). Formation of a triterpene dimer via a linker bearing triazole (70) dramatically increased its potency with IC50 at similar to 10 nM. Mechanistically, such functional triterpenes interrupt the interaction between HCV envelope protein E2 and its receptor CD81 via binding to E2, thus blocking virus and host cell recognition. This study establishes the importance of triterpene natural products as new leads for the development of potential HCV entry inhibitors.