2,4-diamino-7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine | 170468-37-8

• 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: 2,4-diamino-7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine
• 英文别名: T70080；7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-2,4-diamine；2,4-diamino-7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine；(2R,3R,4S,5R)-5-(2,4-diaminopyrrolo[2,3-d]pyrimidin-7-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol；(2R,3R,4S,5R)-5-(2,4-diaminopyrrolo[2,3-d]pyrimidin-7-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• CAS: 170468-37-8
• 化学式: C₁₁H₁₄FN₅O₃
• 分子量: 283.262
• InChiKey: ATOWTVMXURUQQI-JTGULSINSA-N

物化性质

• 熔点：
  188 °C(Solv: methanol (67-56-1))
• 沸点：
  718.3±70.0 °C(Predicted)
• 密度：
  1.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2,4-diamino-7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine 在 溶剂黄146 、 sodium nitrite 作用下， 反应 2.5h， 以69%的产率得到4-amino-7-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  卤代7-脱氮嘌呤核苷：2'-脱氧-2'-氟-β-D-阿拉伯糖核苷的立体选择性合成和构象。

  摘要：

  5-卤代7-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）-7H-吡咯并[2,3-d]嘧啶核苷3b-d，4a-c和7-脱氮的立体选择性合成描述了-2'-脱氧异鸟苷。2-氨基-4-氯-7H-吡咯并[2,3-d]嘧啶（5）与3,5-二-O-苯甲酰基-2-脱氧-2-氟-α-D-阿拉伯呋喃糖基的核碱基阴离子糖基化溴化物（6）仅生成β-D-异头物，将其解封（-> 8），在C4处进行胺化（-> 3a），然后在C2处进行选择性脱氨，生成2'-脱氧-2'-氟-β -D-阿拉伯呋喃糖基7-脱氮异鸟嘌呤（2）。5-卤代的4-氯-2-新戊酰基氨基-7H-吡咯并[2，3-d]嘧啶9a-c与6的缩合提供了N7-核苷10a-c以及N2，N7-双糖基化的化合物11a-c。前者转化为相应的2,4-二氨基化合物3b-d，后者用NaOMe / MeOH解封闭，得到4-甲氧基-核苷4a-c。基于邻位[1H，1H]偶合常数对核苷2

  DOI：

  10.1039/b409648g
• 作为产物：
  描述：

  2-氨基-4-氯吡咯并[2,3-d]嘧啶 在 氨 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 169.0h， 生成 2,4-diamino-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

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.
• Halogenated 7-deazapurine nucleosides: stereoselective synthesis and conformation of 2′-deoxy-2′-fluoro-β-<scp>d</scp>-arabinonucleosides
  作者：Xiaohua Peng、Frank Seela

  DOI：10.1039/b409648g

  日期：——

  The stereoselective syntheses of 5-halogenated 7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine nucleosides 3b-d, 4a-c as well as 7-deaza-2'-deoxyisoguanosine are described. Nucleobase anion glycosylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (6) exclusively gave the beta-D-anomer, which was

  5-卤代7-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）-7H-吡咯并[2,3-d]嘧啶核苷3b-d，4a-c和7-脱氮的立体选择性合成描述了-2'-脱氧异鸟苷。2-氨基-4-氯-7H-吡咯并[2,3-d]嘧啶（5）与3,5-二-O-苯甲酰基-2-脱氧-2-氟-α-D-阿拉伯呋喃糖基的核碱基阴离子糖基化溴化物（6）仅生成β-D-异头物，将其解封（-> 8），在C4处进行胺化（-> 3a），然后在C2处进行选择性脱氨，生成2'-脱氧-2'-氟-β -D-阿拉伯呋喃糖基7-脱氮异鸟嘌呤（2）。5-卤代的4-氯-2-新戊酰基氨基-7H-吡咯并[2，3-d]嘧啶9a-c与6的缩合提供了N7-核苷10a-c以及N2，N7-双糖基化的化合物11a-c。前者转化为相应的2,4-二氨基化合物3b-d，后者用NaOMe / MeOH解封闭，得到4-甲氧基-核苷4a-c。基于邻位[1H，1H]偶合常数对核苷2