N-[(3β)-3-acetyloxy-lup-20(29)-en-28-oyl]-1,1-dimethylethyl-(2-aminoethyl)carbamate | 1426661-55-3

• 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: N-[(3β)-3-acetyloxy-lup-20(29)-en-28-oyl]-1,1-dimethylethyl-(2-aminoethyl)carbamate
• 英文别名: tert-butyl (2-{[(3β)-3-acetoxy-28-oxolup-20(29)-en-28-yl]amino}ethyl)carbamate；N-(O3-acetyl-betulinyl)-N'-boc-ethylenediamine；[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylcarbamoyl]-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] acetate
• CAS: 1426661-55-3
• 化学式: C₃₉H₆₄N₂O₅
• 分子量: 640.948
• InChiKey: WZCGCKVHKAZMJW-DJLUIXQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[(3β)-3-acetyloxy-lup-20(29)-en-28-oyl]-1,1-dimethylethyl-(2-aminoethyl)carbamate 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 31.5h， 生成 4-({28-[(2-aminoethyl)amino]-28-oxolup-20,29-en-3β-yl}oxy)-2,2-dimethyl-4-oxobutanoic acid
  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
• 作为产物：
  描述：

  白桦脂酸 在 (benzotriazol-1-yloxy)tripyrrolodinophosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 N-[(3β)-3-acetyloxy-lup-20(29)-en-28-oyl]-1,1-dimethylethyl-(2-aminoethyl)carbamate
  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

• Polyamine derivatives of betulinic acid and β-sitosterol: A comparative investigation
  作者：Uladzimir Bildziukevich、Norbert Vida、Lucie Rárová、Milan Kolář、David Šaman、Libor Havlíček、Pavel Drašar、Zdeněk Wimmer

  DOI：10.1016/j.steroids.2015.04.005

  日期：2015.8

  beta-Sitosterol and betulinic acid were used in designing their conjugates with selected polyamines bearing either an amide bond, or an ester and an amide bond simultaneously in the target molecule. The synthesized compounds were subjected to basic cytotoxic and antimicrobial tests. The synthetic protocol is described separately for each of the three series of the target amides, because each series of compounds required a different synthetic approach. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with the tests on normal human fibroblasts. Most of the target compounds (5a-5c, 11a-11c and 16a-16c) showed medium to high cytotoxicity (0.7-7.8 mu M), however, in some cases the compounds showed high cytotoxicity even toward normal human fibroblasts (11a-11c). Two compounds of this series (11c and 16c) also displayed antimicrobial activity with high and selective microbe specificity. The compound 11c was potent against Escherichia coli (minimal inhibition concentration (MIC) 6.25 mu g mL(-1), i.e. 9.75 nM mL(-1)) and Staphylococcus aureus (MIC 12.5 mu g mL(-1), i.e. 19.5 nM mL(-1)), and showed medium activity against Pseudomonas aeruginosa. The compound 16c was highly active against Enterococcus faecalis and S. aureus (both, MIC 3.125 mu g mL(-1), i.e. 4.22 nM mL(-1)), both Gram-positive bacteria, however showed only weak activity against E. coli and no activity against P. aeruginosa, both Gram-negative bacteria, which indicates possible microbe specificity of 16c. Comparing beta-sitosterol-based series (5a-5c) and betulinic acid series (11a-11c and 16a-16c) of the target compounds, the latter one gave more promising structures. The compounds 11c and 16c showed effects which may be described as multifarious activity (pleiotropic effects). (C) 2015 Elsevier Inc. All rights reserved.
• 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.