methyl N-[N'-(dihydrobetulinic acid-28-oyl)-9-aminononanoyl]-L-glutaminate | 1394157-70-0

• 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: methyl N-[N'-(dihydrobetulinic acid-28-oyl)-9-aminononanoyl]-L-glutaminate
• 英文别名: methyl N-[N'-(betulinic acid-28-oyl)-9-aminononanoyl]-L-glutaminate；methyl (2S)-2-[9-[[(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]nonanoylamino]-5-amino-5-oxopentanoate
• CAS: 1394157-70-0
• 化学式: C₄₅H₇₅N₃O₆
• 分子量: 754.107
• InChiKey: RJEYEERSWUHCKO-MLBBYNKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  54
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  148
• 氢给体数：
  4
• 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 、 methyl N-[N'-(dihydrobetulinic acid-28-oyl)-9-aminononanoyl]-L-glutaminate 在 吡啶 、 4-二甲氨基吡啶 作用下， 以40%的产率得到methyl N-[N'-[3β-O-(3',3'-dimethylsuccinyl)betulinic acid-28-oyl]-9-aminononanoyl]-L-glutaminate
  参考文献：
  名称：

  [EN] 3,28-DISUBSTITUTED BETULINIC ACID DERIVATIVES AS ANTI-HIV AGENTS
  [FR] DÉRIVÉS D'ACIDE BÉTULINIQUE 3,28-DISUBSTITUÉS EN TANT QU'AGENTS ANTI-VIH

  摘要：

  本发明提供了Formula (I)和Formula (II)的化合物，以及含有这些化合物的组合物，以及在治疗HIV等病毒感染中使用它们的方法。

  公开号：

  WO2013148067A1
• 作为产物：
  描述：

  氨基壬酸 在 草酰氯 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 methyl N-[N'-(dihydrobetulinic acid-28-oyl)-9-aminononanoyl]-L-glutaminate
  参考文献：
  名称：

  [EN] 3,28-DISUBSTITUTED BETULINIC ACID DERIVATIVES AS ANTI-HIV AGENTS
  [FR] DÉRIVÉS D'ACIDE BÉTULINIQUE 3,28-DISUBSTITUÉS EN TANT QU'AGENTS ANTI-VIH

  摘要：

  本发明提供了Formula (I)和Formula (II)的化合物，以及含有这些化合物的组合物，以及在治疗HIV等病毒感染中使用它们的方法。

  公开号：

  WO2013148067A1

文献信息

• Synthesis of betulinic acid derivatives as entry inhibitors against HIV-1 and bevirimat-resistant HIV-1 variants
  作者：Zhao Dang、Keduo Qian、Phong Ho、Lei Zhu、Kuo-Hsiung Lee、Li Huang、Chin-Ho Chen

  DOI：10.1016/j.bmcl.2012.06.080

  日期：2012.8

  Betulinic acid derivatives modified at the C28 position are HIV-1entry inhibitors such as compound A43D; however, modified at the C3 position instead of C28 give HIV-1 maturation inhibitor such as bevirimat. Bevirimat exhibited promising pharmacokinetic profiles in clinical trials, but its effectiveness was compromised by the high baseline drug resistance of HIV-1 variants with polymorphism in the putative drug binding site. In an effort to determine whether the viruses with bevirimat resistant polymorphism also altered their sensitivities to the betulinic acid derivatives that inhibit HIV-1 entry, a series of new betulinic acid entry inhibitors were synthesized and tested for their activities against HIV-1 NL4-3 and NL4-3 variants resistant to bevirimat. The results show that the bevirimat resistant viruses were approximately 5- to10-fold more sensitive to three new glutamine ester derivatives (13, 15 and 38) and A43D in an HIV-1 multi-cycle replication assay. In contrast, the wild type NL4-3 and the bevirimat resistant variants were equally sensitive to the HIV-1 RT inhibitor AZT. In addition, these three new compounds markedly improved microsomal stability compared to A43D. (c) 2012 Elsevier Ltd. All rights reserved.
• 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.
• [EN] 3,28-DISUBSTITUTED BETULINIC ACID DERIVATIVES AS ANTI-HIV AGENTS<br/>[FR] DÉRIVÉS D'ACIDE BÉTULINIQUE 3,28-DISUBSTITUÉS EN TANT QU'AGENTS ANTI-VIH
  申请人：UNIV NORTH CAROLINA

  公开号：WO2013148067A1

  公开（公告）日：2013-10-03

  The present invention provides compounds of Formula (I) and Formula (II): along with compositions containing the same and methods of use thereof in treating viral infections such as HIV infections.

  本发明提供了Formula (I)和Formula (II)的化合物，以及含有这些化合物的组合物，以及在治疗HIV等病毒感染中使用它们的方法。