Acetic acid (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(9-amino-nonylcarbamoyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-9-yl ester | 882505-90-0

• 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: Acetic acid (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(9-amino-nonylcarbamoyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-9-yl ester
• 英文别名: [(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(9-aminononylcarbamoyl)-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] acetate
• CAS: 882505-90-0
• 化学式: C₄₁H₇₀N₂O₃
• 分子量: 639.018
• InChiKey: AXJYNTCRQUJFFO-ICIQEZEZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Acetic acid (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(9-amino-nonylcarbamoyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-9-yl ester 在 吡啶 、 4-二甲氨基吡啶 、 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 2.0h， 生成 4-[[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-[9-[[(2S)-5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoyl]amino]nonylcarbamoyl]-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 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 Acetic acid (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(9-amino-nonylcarbamoyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-9-yl ester
  参考文献：
  名称：

  双功能桦木酸衍生物的合成及其抗HIV活性。

  摘要：

  在C-3处带有侧链的桦木酸（BA）衍生物可以抑制HIV-1的成熟。另一方面，在C-28带有侧链的BA衍生物可以阻止HIV-1进入。为了在单个分子中结合抗成熟和抗进入活性，已经合成了在C-3和C-28处含有侧链的新的双功能BA衍生物。最有效的化合物（[[[N- [3beta-O-（3'，3'-二甲基琥珀酰基）-lup-20（29）-en-28-oyl] -7-氨基庚基] -carba moyl]甲烷抑制HIV -1在EC26为0.0026 microM时，效力至少是抗成熟铅化合物DSB或抗进入铅化合物IC9564的20倍。这种双功能BA衍生物对HIV的进入和成熟均具有活性。

  DOI：

  10.1016/j.bmc.2005.11.016

文献信息

• [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。
• 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.