N²-[3β-(3-carboxy-3-methylbutanoyloxy)lup-20,29-en-28-oyl]-L-lysine | 1426661-86-0

• 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: N²-[3β-(3-carboxy-3-methylbutanoyloxy)lup-20,29-en-28-oyl]-L-lysine
• 英文别名: N²-[(3β)-3-(3-carboxy-3-methylbutanoyloxy)lup-20(29)-en-28-oyl]-L-lysine；4-[[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-[[(1S)-5-amino-1-carboxypentyl]carbamoyl]-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid
• CAS: 1426661-86-0
• 化学式: C₄₂H₆₈N₂O₇
• 分子量: 713.011
• InChiKey: CZQZRZWROKSUMN-HMDNUBJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  51
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3Beta-乙酰氧基白桦酸 在 盐酸 、 4-二甲氨基吡啶 、 (benzotriazol-1-yloxy)tripyrrolodinophosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 103.0h， 生成 N²-[3β-(3-carboxy-3-methylbutanoyloxy)lup-20,29-en-28-oyl]-L-lysine
  参考文献：
  名称：

  Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site

  摘要：

  Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction. Moreover, its low hydrosolubility makes it difficult to study its interaction with the CA-SP1 junction. We have synthesized new derivatives of bevirimat by adding different hydrophilic substituents at the C-28 position to improve their hydrosolubility and perform the structural study of a complex by NMR. Synthesis of the new derivatives, the effect of substituents at the C-28 position and their hydrosolubility are discussed. The ability of these molecules to inhibit viral infection and their cytotoxicity is assessed. Compared to the well-known bevirimat (2), one of our compounds (16) shows a higher hydrosolubility associated with a 2.5 fold increase in activity, a higher selectivity index and a better antiviral profile. Moreover, for the first time a direct interaction between a derivative of bevirimat (16) and the domain CA-SP1 NC is shown by NMR. Information from this study should allow us to decipher the mechanism by which bevirimat inhibits HIV-1 maturation and how the natural polymorphism of the spacer peptide SP1 triggers resistance to inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.013

文献信息

• Derivatives of 3-O-(3',3'-dimethylsuccinyl)-betulinic acid
  申请人：Centre National de la Recherche Scientifique (CNRS)

  公开号：EP2567965B1

  公开（公告）日：2015-09-02
• Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site
  作者：Pascale Coric、Serge Turcaud、Florence Souquet、Laurence Briant、Bernard Gay、Jacques Royer、Nathalie Chazal、Serge Bouaziz

  DOI：10.1016/j.ejmech.2013.01.013

  日期：2013.4

  Bevirimat (2), the first-in-class HIV-1 maturation inhibitor, shows a low efficacy due essentially to the natural polymorphism of its target, the CA-SP1 junction. Moreover, its low hydrosolubility makes it difficult to study its interaction with the CA-SP1 junction. We have synthesized new derivatives of bevirimat by adding different hydrophilic substituents at the C-28 position to improve their hydrosolubility and perform the structural study of a complex by NMR. Synthesis of the new derivatives, the effect of substituents at the C-28 position and their hydrosolubility are discussed. The ability of these molecules to inhibit viral infection and their cytotoxicity is assessed. Compared to the well-known bevirimat (2), one of our compounds (16) shows a higher hydrosolubility associated with a 2.5 fold increase in activity, a higher selectivity index and a better antiviral profile. Moreover, for the first time a direct interaction between a derivative of bevirimat (16) and the domain CA-SP1 NC is shown by NMR. Information from this study should allow us to decipher the mechanism by which bevirimat inhibits HIV-1 maturation and how the natural polymorphism of the spacer peptide SP1 triggers resistance to inhibitors. (C) 2013 Elsevier Masson SAS. All rights reserved.