3TC 5′-ethoxycarbonyl phosphonate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 3TC 5′-ethoxycarbonyl phosphonate
• 英文别名: [(2R,5S)-5-(4-amino-2-oxopyrimidin-1-yl)-1,3-oxathiolan-2-yl]methoxy-ethoxycarbonylphosphinic acid
• 化学式: C₁₁H₁₆N₃O₇PS
• 分子量: 365.304
• InChiKey: KPSFSKZFNZNTMH-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  166
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3TC 5′-ethoxycarbonyl phosphonate 在 ammonium hydroxide 作用下， 反应 18.0h， 以96%的产率得到3TC 5′-aminocarbonyl phosphonate
  参考文献：
  名称：

  A new antiviral: Chimeric 3TC–AZT phosphonate efficiently inhibits HIV-1 in human tissues ex vivo

  摘要：

  Although more-recently developed antivirals target different molecules in the HIV-1 replication cycle, nucleoside reverse transcriptase inhibitors (NRTIs) remain central for HIV-1 therapy. Here, we test the anti-HIV activity of a phosphonate chimera of two well-known NRTIs, namely AZT and 3TC. We show that this newly synthesized compound suppressed HIV-1 infection in lymphoid tissue ex vivo more efficiently than did other phosphonates of NRTIs. Moreover, the new compound was not toxic for tissue cells, thus making the chimeric phosphonate strategy a valid approach for the development of anti HIV-1 compound heterodimers.

  DOI：

  10.1016/j.antiviral.2014.06.019
• 作为产物：
  描述：

  ethoxycarbonylphosphonic acid 、 拉米夫定 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以73%的产率得到3TC 5′-ethoxycarbonyl phosphonate
  参考文献：
  名称：

  A new antiviral: Chimeric 3TC–AZT phosphonate efficiently inhibits HIV-1 in human tissues ex vivo

  摘要：

  Although more-recently developed antivirals target different molecules in the HIV-1 replication cycle, nucleoside reverse transcriptase inhibitors (NRTIs) remain central for HIV-1 therapy. Here, we test the anti-HIV activity of a phosphonate chimera of two well-known NRTIs, namely AZT and 3TC. We show that this newly synthesized compound suppressed HIV-1 infection in lymphoid tissue ex vivo more efficiently than did other phosphonates of NRTIs. Moreover, the new compound was not toxic for tissue cells, thus making the chimeric phosphonate strategy a valid approach for the development of anti HIV-1 compound heterodimers.

  DOI：

  10.1016/j.antiviral.2014.06.019

文献信息

• Inhibition of Human Immunodeficiency Virus Type 1 Replication by Phosphonoformate- and Phosphonoacetate-2',3'-Dideoxy-3'-thiacytidine Conjugates
  作者：Anne-Sophie Charvet、Michel Camplo、Philippe Faury、Jean-Christophe Graciet、Nicolas Mourier、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1021/jm00040a014

  日期：1994.7

  The synthesis of potential ''combined prodrugs'' where phosphonoformic acid (PFA) or phosphonoacetic acid (PAA) was attached to the 5'-O or N-4 position of 2',3'-dideoxy-3'-thiacytidine (BCH-189) is described. The anti-HIV-1 activity of 11 analogues which included carboxylic ester or phosphoric ester linkages of PFA or PAA to BCH-189 was determined in MT-4 cells. Of these compounds, the IC50 Of analogues 3, 4, 6, and 7 ranged from 0.2 to 100 mu M, while IC50 for BCH-189 in this system was 0.1 mu M. In vitro hydrolysis of the various esters or amides in human plasma indicated that these agents were relatively stable in the presence of plasma esterases with t(1/2) values of up to 120 min. Moreover, lipophilicity of these compounds (partition coefficient) was determined in order to establish correlation between lipophilicity and diffusion of BCH-189 analogues into the cells. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agent BCH-189, but intrinsic anti-HIV-1 activity of some of PAA and PFA adducts, themselves, may also be involved.
• A new antiviral: Chimeric 3TC–AZT phosphonate efficiently inhibits HIV-1 in human tissues ex vivo
  作者：Christophe Vanpouille、Anastasia Khandazhinskaya、Inna Karpenko、Sonia Zicari、Victor Barreto-de-Souza、Svetlana Frolova、Leonid Margolis、Sergey Kochetkov

  DOI：10.1016/j.antiviral.2014.06.019

  日期：2014.9

  Although more-recently developed antivirals target different molecules in the HIV-1 replication cycle, nucleoside reverse transcriptase inhibitors (NRTIs) remain central for HIV-1 therapy. Here, we test the anti-HIV activity of a phosphonate chimera of two well-known NRTIs, namely AZT and 3TC. We show that this newly synthesized compound suppressed HIV-1 infection in lymphoid tissue ex vivo more efficiently than did other phosphonates of NRTIs. Moreover, the new compound was not toxic for tissue cells, thus making the chimeric phosphonate strategy a valid approach for the development of anti HIV-1 compound heterodimers.