N-[(3β,4α,9β,16α,20S)-20-(dimethylamino)-16-hydroxy-4-(hydroxymethyl)-4,14-dimethyl-11-oxo-9,19-cyclopregnan-3-yl]-2-methylpropanamide

• 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: N-[(3β,4α,9β,16α,20S)-20-(dimethylamino)-16-hydroxy-4-(hydroxymethyl)-4,14-dimethyl-11-oxo-9,19-cyclopregnan-3-yl]-2-methylpropanamide
• 英文别名: N-3-iso-butyrylcycloxobuxidine F；N-3-isobutyrylcycloxobuxidine-F；(20S)-3-isobutyrylamino-9,19-cyclo-4α-hydroxymethyl-4,14α-dimethyl-20-dimethylamino-5α,9-pregnan-16α-ol-11-one；N-3-isobutyrylcycloxobuxidine-F, 2；N-[(1R,3R,6S,7S,8R,11S,12S,14R,15S,16R)-15-[(1S)-1-(dimethylamino)ethyl]-14-hydroxy-7-(hydroxymethyl)-7,12,16-trimethyl-18-oxo-6-pentacyclo[9.7.0.01,3.03,8.012,16]octadecanyl]-2-methylpropanamide
• 化学式: C₃₀H₅₀N₂O₄
• 分子量: 502.738
• InChiKey: PZQLEQUEGAJQMS-PDIVMOMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[(3β,4α,9β,16α,20S)-20-(dimethylamino)-16-hydroxy-4-(hydroxymethyl)-4,14-dimethyl-11-oxo-9,19-cyclopregnan-3-yl]-2-methylpropanamide 在 吡啶 、 magnesium sulfate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 53.5h， 生成 (20S)-16α-acetyl-3-isobutyrylamino-9,19-cyclo-4α-hydroxytosylmethyl-4,14α-dimethyl-20-dimethylamino-5α,9-pregnan-11-one
  参考文献：
  名称：

  TETRACYCLIC TERPENE SERIES COMPOUNDS, METHODS FOR PREPARING SAME, USES THEREOF AS MEDICINES AND PHARMACEUTICAL COMPOUNDS CONTAINING SAME

  摘要：

  这项发明涉及一种通式（I）的三萜生物碱。该发明还涉及制备该化合物的方法以及将其用作药物的用途。

  公开号：

  US20120040930A1

文献信息

• New Potent Acetylcholinesterase Inhibitors in the Tetracyclic Triterpene Series
  作者：Thibault Sauvaître、Mireille Barlier、Denyse Herlem、Nohad Gresh、Angèle Chiaroni、Daniel Guenard、Catherine Guillou

  DOI：10.1021/jm070536w

  日期：2007.11.1

  A new highly selective inhibitor of acetylcholinesterase (AChE) was discovered by high-throughput screening. Compound 1 was synthesized from a natural product, the N-3-isobutyrylcycloxobuxidine-F 2. A new extraction protocol of this compound is described. The hemisynthesis and optimization of 1 are reported. The analogs of 1 were tested in vitro for the inhibition of both cholinesterases (AChE and

  通过高通量筛选发现了一种新的高选择性乙酰胆碱酯酶（AChE）抑制剂。化合物1是从天然产物N-3-异丁酰基环xuxuxidine-F 2合成的。描述了该化合物的新提取方法。报告了1的半合成和优化。在体外测试了1的类似物对两种胆碱酯酶（AChE和BuChE）的抑制作用。这些化合物选择性抑制AChE。使用Discover Biosym软件对2和AChE进行了广泛的分子对接研究，以使结合相互作用合理化。结果表明，配体2同时与AChE的催化位点和外围位点结合。
• New potent human acetylcholinesterase inhibitors in the tetracyclic triterpene series with inhibitory potency on amyloid β aggregation
  作者：Julien Rouleau、Bogdan I. Iorga、Catherine Guillou

  DOI：10.1016/j.ejmech.2011.02.073

  日期：2011.6

  New acetylcholinesterase inhibitors in the tetracyclic triterpene series were synthesized, tested in vitro for the inhibition of cholinesterases (different sources of AChE and BuChE) and for the ability to prevent AChE-induced A beta aggregation. Some compounds have hAChE IC50 values in the nanomolar range and showed ability to block the AChE-induced A beta aggregation. The mode of interaction between EeAChE and compounds 1 and 36e was investigated using docking and molecular dynamics simulations. These studies suggested that both compounds interact simultaneously with the catalytic and the peripheral sites of AChE, and the nature of protein-ligand interactions is mainly hydrophobic. (C) 2011 Elsevier Masson SAS. All rights reserved.
• TETRACYCLIC TERPENE SERIES COMPOUNDS, METHODS FOR PREPARING SAME, USES THEREOF AS MEDICINES AND PHARMACEUTICAL COMPOUNDS CONTAINING SAME
  申请人：Guillou Catherine

  公开号：US20120040930A1

  公开（公告）日：2012-02-16

  The invention concerns a triterpene alkaloid of general formula (I). The invention also concerns a method for making same and use thereof as medicine.

  这项发明涉及一种通式（I）的三萜生物碱。该发明还涉及制备该化合物的方法以及将其用作药物的用途。