3-((2S,3S,3aR,9aR)-5,5,7,7-Tetraisopropyl-3-trimethylsilanyloxy-tetrahydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-ylamine | 96807-07-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 3-((2S,3S,3aR,9aR)-5,5,7,7-Tetraisopropyl-3-trimethylsilanyloxy-tetrahydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-ylamine
• CAS: 96807-07-7
• 化学式: C₂₅H₄₇N₅O₅Si₃
• 分子量: 581.935
• InChiKey: FZNCEJTYYJRADC-LZQXYRQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.55
• 重原子数：
  38.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  126.63
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3-((2S,3S,3aR,9aR)-5,5,7,7-Tetraisopropyl-3-trimethylsilanyloxy-tetrahydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-ylamine 在 2,2'-azobisbutyronitrile 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 生成 2'-deoxyformycin A
  参考文献：
  名称：

  Improved synthesis of 2'-deoxyformycin A and studies of its in vitro activity against mouse lymphoma of T-cell origin

  摘要：

  7-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine (2'-deoxyformycin A) was synthesized from formycin A by a sequence consisting of (i) 3',5'-cyclosilylation with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, (ii) 2'-acylation with phenoxythiocarbonyl chloride and 4-(N,N-dimethylamino)pyridine, (iii) N-trimethylsilylation with hexamethyldisilazane, (iv) reduction of the 2'-O-phenoxythiocarbonyl group with tri-n-butyltin hydride, and (v) desilylation with tetra-n-butylammonium fluoride. 2'-Deoxyformycin A was a potent inhibitor of the in vitro growth of S49 lymphoma, a murine tumor of T-cell origin. The IC50 of 2'-deoxyformycin A against S49 cells was 10-15 microM, whereas that of 2'-deoxyadenosine (dAdo) under the same conditions (72-h incubation in medium containing heat-inactivated horse serum) was 180 microM. In the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to block intracellular adenosine deaminase (ADA) activity, 2'-deoxyformycin A and dAdo both gave IC50's of 5-10 microM. When assayed against a mutant S49 subline lacking adenosine kinase (AK) or a subline with a combined deletion of AK and deoxycytidine kinase (dCK), 2'-deoxyformycin A in combination with 10 microM EHNA was inactive at concentrations of up to 50 microM. Similar lack of activity against kinase-deficient cells was shown by formycin A. Thus, phosphorylation of 2'-deoxyformycin A appears to be required for biological activity and is probably catalyzed by AK rather than dCK. 2'-Deoxyformycin A and related 2'-deoxyribo-C-nucleoside analogues of the purine type may be of interest as potential T-cell specific cytotoxic agents.

  DOI：

  10.1021/jm00146a020
• 作为产物：
  描述：

  7-amino-3-<3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-β-D-ribofuranosyl>pyrazolo<4,3-d>pyrimidine 在 4-二甲氨基吡啶 、 硫酸氢铵 作用下， 以 乙腈 为溶剂， 反应 25.0h， 生成 3-((2S,3S,3aR,9aR)-5,5,7,7-Tetraisopropyl-3-trimethylsilanyloxy-tetrahydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-ylamine
  参考文献：
  名称：

  Improved synthesis of 2'-deoxyformycin A and studies of its in vitro activity against mouse lymphoma of T-cell origin

  摘要：

  7-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine (2'-deoxyformycin A) was synthesized from formycin A by a sequence consisting of (i) 3',5'-cyclosilylation with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, (ii) 2'-acylation with phenoxythiocarbonyl chloride and 4-(N,N-dimethylamino)pyridine, (iii) N-trimethylsilylation with hexamethyldisilazane, (iv) reduction of the 2'-O-phenoxythiocarbonyl group with tri-n-butyltin hydride, and (v) desilylation with tetra-n-butylammonium fluoride. 2'-Deoxyformycin A was a potent inhibitor of the in vitro growth of S49 lymphoma, a murine tumor of T-cell origin. The IC50 of 2'-deoxyformycin A against S49 cells was 10-15 microM, whereas that of 2'-deoxyadenosine (dAdo) under the same conditions (72-h incubation in medium containing heat-inactivated horse serum) was 180 microM. In the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to block intracellular adenosine deaminase (ADA) activity, 2'-deoxyformycin A and dAdo both gave IC50's of 5-10 microM. When assayed against a mutant S49 subline lacking adenosine kinase (AK) or a subline with a combined deletion of AK and deoxycytidine kinase (dCK), 2'-deoxyformycin A in combination with 10 microM EHNA was inactive at concentrations of up to 50 microM. Similar lack of activity against kinase-deficient cells was shown by formycin A. Thus, phosphorylation of 2'-deoxyformycin A appears to be required for biological activity and is probably catalyzed by AK rather than dCK. 2'-Deoxyformycin A and related 2'-deoxyribo-C-nucleoside analogues of the purine type may be of interest as potential T-cell specific cytotoxic agents.

  DOI：

  10.1021/jm00146a020