4-amino-5-cyano-7-(2-deoxy-2-bromo-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine | 127913-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-amino-5-cyano-7-(2-deoxy-2-bromo-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine
• 英文别名: 4-amino-5-cyano-7-(2-deoxy-2-bromo-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine；4-Amino-7-(3-bromo-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-7H-pyrrolo(2,3-d)pyrimidine-5-carbonitrile；4-amino-7-[(2R,3S,4R,5R)-3-bromo-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 127913-81-9
• 化学式: C₁₂H₁₂BrN₅O₃
• 分子量: 354.163
• InChiKey: PVKOGOYWCPHLFZ-IQEPQDSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-amino-5-cyano-7-(2-deoxy-2-bromo-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine 在 ammonium hydroxide 、 双氧水 作用下， 以 甲醇 为溶剂， 反应 0.85h， 以86%的产率得到4-氨基-7-(2-溴-2-脱氧-β-D-呋喃阿拉伯糖基)-7H-吡咯并[2,3-d]嘧啶-5-甲酰胺
  参考文献：
  名称：

  Arabinofuranosylpyrrolo[2,3-d]pyrimidines as potential agents for human cytomegalovirus infections

  摘要：

  Protection of the 3'- and 5'-hydroxyl groups of the nucleoside antibiotic toyocamycin (1) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane was followed by (trifluoromethyl)sulfonylation of the 2'-hydroxyl group. A displacement of the resulting triflate ester moiety with lithium chloride, lithium bromide, sodium iodide, and lithium azide in hexamethylphosphoramide was followed by a removal of the disilyl moiety with tetra-n-butylammonium fluoride to afford the appropriate (2'-deoxy-2'-substituted-arabinofuranosyl)toyocamycin analogues 6a-d. Hydrolysis of the carbonitrile moieties of 6a-d with hydrogen peroxide gave the corresponding sangivamycin analogues (7a-d). A reduction of the azido moiety of 6a and 7a with 1,3-propanedithiol furnished the corresponding amino derivatives (6e and 7e). The antiproliferative activity of 6a-e and 7a-e was evaluated in L1210 cell cultures. None of these compounds caused significant inhibition of cell growth. Evaluation of these compounds for antiviral activity showed that all the toyocamycin analogues were active against human CMV, but of the sangivamycin analogues, only (2'-deoxy-2'-azidoarabinosyl)sangivamycin (7a) was active against this virus. None of the compounds were active against HSV-1 or HSV-2. (2'-Deoxy-2'-aminoarabinofuranosyl)toyocamycin (6e) was studied more extensively and showed some separation between antiviral activity and cytotoxicity as measured by effects on DNA synthesis, cell growth, and cell-plating efficiency. Although 6e also was active against murine CMV in vitro, it was not active against this virus in infected mice. We conclude that arabinosylpyrrolopyrimidines have potential as antivirals, but no members of the current series are potent enough to show significant activity in vivo.

  DOI：

  10.1021/jm00174a011
• 作为产物：
  描述：

  4-amino-5-cyano-7-<3,5-O-<1,1,3,3-tetrakis(methylethyl)disiloxan-1,3-diyl>-β-D-ribofuranosyl>pyrrolo<2,3-d>pyrimidine 在 4-二甲氨基吡啶 、 四丁基氟化铵 、 lithium bromide 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 1,2-二氯乙烷 为溶剂， 反应 3.17h， 生成 4-amino-5-cyano-7-(2-deoxy-2-bromo-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  Arabinofuranosylpyrrolo[2,3-d]pyrimidines as potential agents for human cytomegalovirus infections

  摘要：

  Protection of the 3'- and 5'-hydroxyl groups of the nucleoside antibiotic toyocamycin (1) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane was followed by (trifluoromethyl)sulfonylation of the 2'-hydroxyl group. A displacement of the resulting triflate ester moiety with lithium chloride, lithium bromide, sodium iodide, and lithium azide in hexamethylphosphoramide was followed by a removal of the disilyl moiety with tetra-n-butylammonium fluoride to afford the appropriate (2'-deoxy-2'-substituted-arabinofuranosyl)toyocamycin analogues 6a-d. Hydrolysis of the carbonitrile moieties of 6a-d with hydrogen peroxide gave the corresponding sangivamycin analogues (7a-d). A reduction of the azido moiety of 6a and 7a with 1,3-propanedithiol furnished the corresponding amino derivatives (6e and 7e). The antiproliferative activity of 6a-e and 7a-e was evaluated in L1210 cell cultures. None of these compounds caused significant inhibition of cell growth. Evaluation of these compounds for antiviral activity showed that all the toyocamycin analogues were active against human CMV, but of the sangivamycin analogues, only (2'-deoxy-2'-azidoarabinosyl)sangivamycin (7a) was active against this virus. None of the compounds were active against HSV-1 or HSV-2. (2'-Deoxy-2'-aminoarabinofuranosyl)toyocamycin (6e) was studied more extensively and showed some separation between antiviral activity and cytotoxicity as measured by effects on DNA synthesis, cell growth, and cell-plating efficiency. Although 6e also was active against murine CMV in vitro, it was not active against this virus in infected mice. We conclude that arabinosylpyrrolopyrimidines have potential as antivirals, but no members of the current series are potent enough to show significant activity in vivo.

  DOI：

  10.1021/jm00174a011

文献信息

• KRAWCZYK, STEVEN H.;BERNIER-RODRIGUEZ, MARTHA;NASSIRI, REZA M.;KERN, EARL+, J. MED. CHEM., 33,(1990) N2, C. 3160-3169
  作者：KRAWCZYK, STEVEN H.、BERNIER-RODRIGUEZ, MARTHA、NASSIRI, REZA M.、KERN, EARL+

  DOI：——

  日期：——
• Arabinofuranosylpyrrolo[2,3-d]pyrimidines as potential agents for human cytomegalovirus infections
  作者：Steven H. Krawczyk、Martha Bernier-Rodriguez、M. Reza Nassiri、Earl R. Kern、Linda L. Wotring、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm00174a011

  日期：1990.12

  Protection of the 3'- and 5'-hydroxyl groups of the nucleoside antibiotic toyocamycin (1) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane was followed by (trifluoromethyl)sulfonylation of the 2'-hydroxyl group. A displacement of the resulting triflate ester moiety with lithium chloride, lithium bromide, sodium iodide, and lithium azide in hexamethylphosphoramide was followed by a removal of the disilyl moiety with tetra-n-butylammonium fluoride to afford the appropriate (2'-deoxy-2'-substituted-arabinofuranosyl)toyocamycin analogues 6a-d. Hydrolysis of the carbonitrile moieties of 6a-d with hydrogen peroxide gave the corresponding sangivamycin analogues (7a-d). A reduction of the azido moiety of 6a and 7a with 1,3-propanedithiol furnished the corresponding amino derivatives (6e and 7e). The antiproliferative activity of 6a-e and 7a-e was evaluated in L1210 cell cultures. None of these compounds caused significant inhibition of cell growth. Evaluation of these compounds for antiviral activity showed that all the toyocamycin analogues were active against human CMV, but of the sangivamycin analogues, only (2'-deoxy-2'-azidoarabinosyl)sangivamycin (7a) was active against this virus. None of the compounds were active against HSV-1 or HSV-2. (2'-Deoxy-2'-aminoarabinofuranosyl)toyocamycin (6e) was studied more extensively and showed some separation between antiviral activity and cytotoxicity as measured by effects on DNA synthesis, cell growth, and cell-plating efficiency. Although 6e also was active against murine CMV in vitro, it was not active against this virus in infected mice. We conclude that arabinosylpyrrolopyrimidines have potential as antivirals, but no members of the current series are potent enough to show significant activity in vivo.