N-[N'-(betulinic acid-28-oyl)-8-aminooctyl]-Nα-Boc-L-glutaminamide | 1394157-62-0

• 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: N-[N'-(betulinic acid-28-oyl)-8-aminooctyl]-Nα-Boc-L-glutaminamide
• 英文别名: tert-butyl N-[(2S)-1-[8-[[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-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]chrysene-3a-carbonyl]amino]octylamino]-5-amino-1,5-dioxopentan-2-yl]carbamate
• CAS: 1394157-62-0
• 化学式: C₄₈H₈₂N₄O₆
• 分子量: 811.202
• InChiKey: VRFGENFMIXMBOY-SUDPWZNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.8
• 重原子数：
  58
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  160
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,2-二甲基琥珀酸酐 、 N-[N'-(betulinic acid-28-oyl)-8-aminooctyl]-Nα-Boc-L-glutaminamide 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 2.0h， 以35%的产率得到4-[[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-[8-[[(2S)-5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoyl]amino]octylcarbamoyl]-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-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-oxo-butanoic acid
  参考文献：
  名称：

  New Betulinic Acid Derivatives for Bevirimat-Resistant Human Immunodeficiency Virus Type-1

  摘要：

  Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.

  DOI：

  10.1021/jm3016969
• 作为产物：
  描述：

  (3β)-N-(8-aminooctyl)-3-acetyloxy-lup-20(29)-en-28-amide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 N-[N'-(betulinic acid-28-oyl)-8-aminooctyl]-Nα-Boc-L-glutaminamide
  参考文献：
  名称：

  New Betulinic Acid Derivatives for Bevirimat-Resistant Human Immunodeficiency Virus Type-1

  摘要：

  Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.

  DOI：

  10.1021/jm3016969

文献信息

• New Betulinic Acid Derivatives for Bevirimat-Resistant Human Immunodeficiency Virus Type-1
  作者：Zhao Dang、Phong Ho、Lei Zhu、Keduo Qian、Kuo-Hsiung Lee、Li Huang、Chin-Ho Chen

  DOI：10.1021/jm3016969

  日期：2013.3.14

  Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.