4-amino-5-cyano-7-(2-deoxy-2-amino-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine | 127880-86-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-amino-5-cyano-7-(2-deoxy-2-amino-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine
• 英文别名: 2'-deoxy-2'-amino-ara-toyocamycin；4-amino-5-cyano-7-(2-deoxy-2-amino-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine；4-Amino-7-(3-amino-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-7H-pyrrolo(2,3-d)pyrimidine-5-carbonitrile；4-amino-7-[(2R,3S,4S,5R)-3-amino-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 127880-86-8
• 化学式: C₁₂H₁₄N₆O₃
• 分子量: 290.282
• InChiKey: FLFLUOVFVHRXJX-IQEPQDSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 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：
  156
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-5-cyano-7-(2-deoxy-2-amino-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine 在 吡啶 、 硫化氢 、 三乙胺 作用下， 反应 16.0h， 以87%的产率得到4-amino-7-(2-deoxy-2-amino-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine-5-thiocarboxamide
  参考文献：
  名称：

  某些硫代桑维霉素类似物的合成和评估，可作为细胞增殖和人巨细胞病毒的潜在抑制剂。

  摘要：

  制备了一系列与核苷丰卡霉素和硫代桑奇霉素有关的7-取代的4-氨基吡咯并[2,3-d]嘧啶，并测试了它们对人巨细胞病毒（HCMV）的活性。核苷2'-脱氧代代霉素（1），木糖-代代霉素（2），3'-脱氧代代霉素（3），2'，3'-脱氧代代-2'，3'-脱氢代代代霉素（4），2'，3'-用就地生成的硫化氢处理二脱氧代代霉素（5），阿拉伯代代霉素（6），2'-脱氧-2'-氨基-代代代霉素（7）和5'-脱氧代代霉素（8）。 thiosangivamycin类似物（9-16）。通过修改文献方法合成氰基衍生物1-8。所有的硫代酰胺衍生物（9-16）均具有抗HCMV的活性，IC50为0.5至6 microM。大多数还对1型单纯疱疹病毒（HSV-1）具有活性，但浓度较高。在两种人类细胞系中，抗病毒活性并未与细胞毒性完全分开。糖基上修饰的位置强烈影响抗增殖活性。与在2'，5'或2'，3'位置进行修饰的木糖基和

  DOI：

  10.1021/jm00020a027
• 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 1,3-丙二硫醇 、 4-二甲氨基吡啶 、 叠氮化锂 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 1,2-二氯乙烷 为溶剂， 反应 9.0h， 生成 4-amino-5-cyano-7-(2-deoxy-2-amino-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：——
• Synthesis and Evaluation of Certain Thiosangivamycin Analogs as Potential Inhibitors of Cell Proliferation and Human Cytomegalovirus
  作者：Steven H. Krawczyk、Thomas E. Renau、M. Reza Nassiri、Allison C. Westerman、Linda L. Wotring、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm00020a027

  日期：1995.9

  7-substituted 4-aminopyrrolo[2,3-d]pyrimidines related to the nucleosides toyocamycin and thiosangivamycin were prepared and tested for their activity against human cytomegalovirus (HCMV). The nucleosides 2'-deoxytoyocamycin (1), xylo-toyocamycin (2), 3'-deoxytoyocamycin (3), 2',3'-dideoxy-2',3'-didehydrotoyocamycin (4), 2',3'-dideoxytoyocamycin (5), ara-toyocamycin (6), 2'-deoxy-2'-amino-ara-toyocamycin

  制备了一系列与核苷丰卡霉素和硫代桑奇霉素有关的7-取代的4-氨基吡咯并[2,3-d]嘧啶，并测试了它们对人巨细胞病毒（HCMV）的活性。核苷2'-脱氧代代霉素（1），木糖-代代霉素（2），3'-脱氧代代霉素（3），2'，3'-脱氧代代-2'，3'-脱氢代代代霉素（4），2'，3'-用就地生成的硫化氢处理二脱氧代代霉素（5），阿拉伯代代霉素（6），2'-脱氧-2'-氨基-代代代霉素（7）和5'-脱氧代代霉素（8）。 thiosangivamycin类似物（9-16）。通过修改文献方法合成氰基衍生物1-8。所有的硫代酰胺衍生物（9-16）均具有抗HCMV的活性，IC50为0.5至6 microM。大多数还对1型单纯疱疹病毒（HSV-1）具有活性，但浓度较高。在两种人类细胞系中，抗病毒活性并未与细胞毒性完全分开。糖基上修饰的位置强烈影响抗增殖活性。与在2'，5'或2'，3'位置进行修饰的木糖基和
• 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.