N-[N'-(betulinic acid-28-oyl)-9-aminononanoyl]-N-methyl-aminoacetonitrile | 1394157-85-7

• 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)-9-aminononanoyl]-N-methyl-aminoacetonitrile
• 英文别名: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-N-[9-[cyanomethyl(methyl)amino]-9-oxononyl]-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-carboxamide
• CAS: 1394157-85-7
• 化学式: C₄₂H₆₉N₃O₃
• 分子量: 664.028
• InChiKey: ZJKQXCRJPINQCU-JEHQWSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  4

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)-9-aminononanoyl]-N-methyl-aminoacetonitrile 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 2.0h， 以39%的产率得到4-[[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-[[9-[cyanomethyl(methyl)amino]-9-oxo-nonyl]carbamoyl]-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：

  3Beta-乙酰氧基白桦酸 在 N-甲基吗啉 、 草酰氯 、 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， 反应 6.0h， 生成 N-[N'-(betulinic acid-28-oyl)-9-aminononanoyl]-N-methyl-aminoacetonitrile
  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.