9-{[(3β)-3-羟基-28-羰基羽扇-20(29)-烯-28-基]氨基}壬烷酸 | 174740-43-3

• 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
• 中文名称: 9-{[(3β)-3-羟基-28-羰基羽扇-20(29)-烯-28-基]氨基}壬烷酸
• 英文名称: N-(3beta-Hydroxylup-20(29)-en-28-oyl)-9-aminonononanoic acid
• 英文别名: 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]nonanoic acid
• CAS: 174740-43-3
• 化学式: C₃₉H₆₅NO₄
• 分子量: 611.949
• InChiKey: VXHANRBEAHCGSY-PPBXDVGMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-{[(3β)-3-羟基-28-羰基羽扇-20(29)-烯-28-基]氨基}壬烷酸 在 N-甲基吗啉 、 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 作用下， 以 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)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-9-oxononyl]carbamoyl]-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]oxy]-2,2-dimethyl-4-oxobutanoic 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：

  3-O-acetylbetulinic acid chloride 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 9-{[(3β)-3-羟基-28-羰基羽扇-20(29)-烯-28-基]氨基}壬烷酸
  参考文献：
  名称：

  Betulinic Acid Derivatives:  A New Class of Specific Inhibitors of Human Immunodeficiency Virus Type 1 Entry

  摘要：

  A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. ''Time of addition'' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.

  DOI：

  10.1021/jm950669u

文献信息

• Betulinic Acid Derivatives:  A New Class of Specific Inhibitors of Human Immunodeficiency Virus Type 1 Entry
  作者：Françoise Soler、Christèle Poujade、Michel Evers、Jean-Christophe Carry、Yvette Hénin、Anne Bousseau、Thierry Huet、Rudi Pauwels、Erik De Clercq、Jean-François Mayaux、Jean-Bernard Le Pecq、Norbert Dereu

  DOI：10.1021/jm950669u

  日期：1996.1.1

  A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. ''Time of addition'' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.
• 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.