cis-2-<<(tert-butyldiphenylsilyl)oxy>methyl>-5-4-(p-tolylsulfonyl)cytosin-1'-yl>-1,3-oxathiolane

• 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: cis-2-<<(tert-butyldiphenylsilyl)oxy>methyl>-5-4-(p-tolylsulfonyl)cytosin-1'-yl>-1,3-oxathiolane
• 英文别名: cis-2-<(tert-butyldiphenyl)silyloxymethyl>-5-4-(tosyl)cytosin-1'-yl>-1,3-oxathiolane；N-[1-[(2S,5R)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-1,3-oxathiolan-5-yl]-2-oxopyrimidin-4-yl]-4-methylbenzenesulfonamide
• 化学式: C₃₁H₃₅N₃O₅S₂Si
• 分子量: 621.854
• InChiKey: XLACWSFYIUFZMQ-WDYNHAJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.52
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  cis-2-<<(tert-butyldiphenylsilyl)oxy>methyl>-5-4-(p-tolylsulfonyl)cytosin-1'-yl>-1,3-oxathiolane 在 lutidine 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 cis-2-(tert-butyldiphenylsilyloxymethyl)-5-4-(CbzTyr-Val-Sta-Ala-Sta-4-aminobutyl)cytosin-1'-yl>-1,3-oxathiolane
  参考文献：
  名称：

  Synthesis and anti-human immunodeficiency virus type 1 activities of new peptido-nucleoside analogues

  摘要：

  In order to investigate whether antiproteasic peptides coupled to anti-reverse transcriptase nucleosides can act as inhibitors at the different stages of the HIV life cycle, various peptido-nucleosides were synthesized using methodologies involving (benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling reagent between the N-4-cytosinyl moiety and the peptide carboxy terminus. The anti-HIV-1 activity in MT(4) cells of this new class of compounds and their anti-HIV protease activities were determined. Fourteen peptido-nucleosides have been synthesized and six act against both the HIV-protease and viral replication in vitro. Although the activity of the most potent compounds against HIV was found to be one order of magnitude lower than that of the parent nucleoside drug 2',3'-dideoxy-3'-thiacytidine, this new class of compound could be of biological interest. Indeed, since the in vitro half-lives (t(1/2)) of the hydrolysis of the most potent compounds in human plasma were found to be longer than 2.5 h, these analogues could reach the infected cells in their structural integrity. This observation does not exclude that these compounds may exert their antiviral effects as combined prodrugs through extracellular or intracellular hydrolysis.

  DOI：

  10.1016/0223-5234(96)88298-5
• 作为产物：
  描述：

  叔丁基二苯基氯硅烷 在 吡啶 作用下， 反应 30.0h， 生成 cis-2-<<(tert-butyldiphenylsilyl)oxy>methyl>-5-4-(p-tolylsulfonyl)cytosin-1'-yl>-1,3-oxathiolane
  参考文献：
  名称：

  Inhibition of Human Immunodeficiency Virus Type 1 Replication by Phosphonoformate- and Phosphonoacetate-2',3'-Dideoxy-3'-thiacytidine Conjugates

  摘要：

  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.

  DOI：

  10.1021/jm00040a014

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.
• Synthesis and anti-human immunodeficiency virus type 1 activities of new peptido-nucleoside analogues
  作者：M Camplo、V Niddam、P Barthélémy、P Faury、N Mourier、V Simon、AS Charvet、C Trabaud、JC Graciet、JC Chermann、JL Kraus

  DOI：10.1016/0223-5234(96)88298-5

  日期：1995.1

  In order to investigate whether antiproteasic peptides coupled to anti-reverse transcriptase nucleosides can act as inhibitors at the different stages of the HIV life cycle, various peptido-nucleosides were synthesized using methodologies involving (benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling reagent between the N-4-cytosinyl moiety and the peptide carboxy terminus. The anti-HIV-1 activity in MT(4) cells of this new class of compounds and their anti-HIV protease activities were determined. Fourteen peptido-nucleosides have been synthesized and six act against both the HIV-protease and viral replication in vitro. Although the activity of the most potent compounds against HIV was found to be one order of magnitude lower than that of the parent nucleoside drug 2',3'-dideoxy-3'-thiacytidine, this new class of compound could be of biological interest. Indeed, since the in vitro half-lives (t(1/2)) of the hydrolysis of the most potent compounds in human plasma were found to be longer than 2.5 h, these analogues could reach the infected cells in their structural integrity. This observation does not exclude that these compounds may exert their antiviral effects as combined prodrugs through extracellular or intracellular hydrolysis.