2-amino-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine | 170468-52-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine
• 英文别名: [(2R,3R,4S,5R)-5-(2-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3-benzoyloxy-4-fluorooxolan-2-yl]methyl benzoate
• CAS: 170468-52-7
• 化学式: C₂₅H₂₁FN₄O₅
• 分子量: 476.464
• InChiKey: BCFHTPHJEYNTBM-XAPVIXHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-amino-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine 在 甲醇 、 氨 作用下， 反应 24.0h， 以94%的产率得到2-amino-7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  Synthesis and Anti-DNA Viral Activities in Vitro of Certain 2,4-Disubstituted- 7-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine Nucleosides

  摘要：

  Several novel 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidines have been synthesized and evaluated for their anti-human cytomegalovirus (HCMV), anti-hepatitis B virus (HBV), and anti-herpes simplex virus (HSV) activities in vitro. These nucleosides were prepared starting from 2-amino-4-chloro-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (3), which in turn was synthesized by direct glycosylation of the sodium salt of 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (1) with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide(2). Displacement of the 4-chloro group of 3 with OH, NH2, NHOH, SH, and SeH nucleophiles furnished the corresponding nucleosides 6-8, 12, and 14, respectively. The 3'-deoxygenation of 2-amino-4-chloro-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (4) and subsequent amination gave 2,4-diamino-2',3'-dideoxy derivative 19. Catalytic hydrogenation of 3 followed by debenzoylation afforded 2-aminopyrrolo[2,3-d]pyrimidine nucleoside 23. Among the compounds evaluated for their ability to inhibit the growth of HCMV (strain AD169) in MRC-5 cells using a plaque reduction assay, only 7 was significantly active in vitro with a 50% inhibitory concentration (IC50) of 3.7 mu g/mL (TI > 125), whereas the IC50 value of ganciclovir (DHPG) was 3.2 mu g/mL. Strain D16 of HCMV was more resistant to 7 (IC50 11 mu g/mL) than the AD169 strain. When 7 was tested in combination with DHPG, the resultant anti-HCMV activity was found to be moderately synergistic with no evidence of antagonism. Nucleoside 7 also reduced episomal HBV replication in human hepatoblastoma 2.2.15 cells with an IC50 of 0.7 mu g/mL (TI > 143). Development of cells harboring HBV which had become resistant to the drug was not observed with 7. Compound 7 also exhibited significant activity against herpes simplex virus types 1 and 2 (IC50 of 4.1 and 6.3 mu g/mL, respectively) in Vero cells.

  DOI：

  10.1021/jm00020a009
• 作为产物：
  描述：

  2-氨基-4-氯吡咯并[2,3-d]嘧啶 在 palladium on activated charcoal ammonium formate 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 25.5h， 生成 2-amino-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  Synthesis and Anti-DNA Viral Activities in Vitro of Certain 2,4-Disubstituted- 7-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine Nucleosides

  摘要：

  Several novel 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidines have been synthesized and evaluated for their anti-human cytomegalovirus (HCMV), anti-hepatitis B virus (HBV), and anti-herpes simplex virus (HSV) activities in vitro. These nucleosides were prepared starting from 2-amino-4-chloro-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (3), which in turn was synthesized by direct glycosylation of the sodium salt of 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (1) with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide(2). Displacement of the 4-chloro group of 3 with OH, NH2, NHOH, SH, and SeH nucleophiles furnished the corresponding nucleosides 6-8, 12, and 14, respectively. The 3'-deoxygenation of 2-amino-4-chloro-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (4) and subsequent amination gave 2,4-diamino-2',3'-dideoxy derivative 19. Catalytic hydrogenation of 3 followed by debenzoylation afforded 2-aminopyrrolo[2,3-d]pyrimidine nucleoside 23. Among the compounds evaluated for their ability to inhibit the growth of HCMV (strain AD169) in MRC-5 cells using a plaque reduction assay, only 7 was significantly active in vitro with a 50% inhibitory concentration (IC50) of 3.7 mu g/mL (TI > 125), whereas the IC50 value of ganciclovir (DHPG) was 3.2 mu g/mL. Strain D16 of HCMV was more resistant to 7 (IC50 11 mu g/mL) than the AD169 strain. When 7 was tested in combination with DHPG, the resultant anti-HCMV activity was found to be moderately synergistic with no evidence of antagonism. Nucleoside 7 also reduced episomal HBV replication in human hepatoblastoma 2.2.15 cells with an IC50 of 0.7 mu g/mL (TI > 143). Development of cells harboring HBV which had become resistant to the drug was not observed with 7. Compound 7 also exhibited significant activity against herpes simplex virus types 1 and 2 (IC50 of 4.1 and 6.3 mu g/mL, respectively) in Vero cells.

  DOI：

  10.1021/jm00020a009

文献信息

• Synthesis and Anti-DNA Viral Activities in Vitro of Certain 2,4-Disubstituted- 7-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine Nucleosides
  作者：Birendra K. Bhattacharya、Joshua O. Ojwang、Robert F. Rando、John H. Huffman、Ganapathi R. Revankar

  DOI：10.1021/jm00020a009

  日期：1995.9

  Several novel 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidines have been synthesized and evaluated for their anti-human cytomegalovirus (HCMV), anti-hepatitis B virus (HBV), and anti-herpes simplex virus (HSV) activities in vitro. These nucleosides were prepared starting from 2-amino-4-chloro-7-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (3), which in turn was synthesized by direct glycosylation of the sodium salt of 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (1) with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide(2). Displacement of the 4-chloro group of 3 with OH, NH2, NHOH, SH, and SeH nucleophiles furnished the corresponding nucleosides 6-8, 12, and 14, respectively. The 3'-deoxygenation of 2-amino-4-chloro-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (4) and subsequent amination gave 2,4-diamino-2',3'-dideoxy derivative 19. Catalytic hydrogenation of 3 followed by debenzoylation afforded 2-aminopyrrolo[2,3-d]pyrimidine nucleoside 23. Among the compounds evaluated for their ability to inhibit the growth of HCMV (strain AD169) in MRC-5 cells using a plaque reduction assay, only 7 was significantly active in vitro with a 50% inhibitory concentration (IC50) of 3.7 mu g/mL (TI > 125), whereas the IC50 value of ganciclovir (DHPG) was 3.2 mu g/mL. Strain D16 of HCMV was more resistant to 7 (IC50 11 mu g/mL) than the AD169 strain. When 7 was tested in combination with DHPG, the resultant anti-HCMV activity was found to be moderately synergistic with no evidence of antagonism. Nucleoside 7 also reduced episomal HBV replication in human hepatoblastoma 2.2.15 cells with an IC50 of 0.7 mu g/mL (TI > 143). Development of cells harboring HBV which had become resistant to the drug was not observed with 7. Compound 7 also exhibited significant activity against herpes simplex virus types 1 and 2 (IC50 of 4.1 and 6.3 mu g/mL, respectively) in Vero cells.