4-amino-5-cyano-7-(5-deoxy-2,3-di-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine | 1054719-24-2

• 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-(5-deoxy-2,3-di-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
• 英文别名: [(2R,3R,4R,5R)-4-acetyloxy-5-(4-amino-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-2-methyloxolan-3-yl] acetate
• CAS: 1054719-24-2
• 化学式: C₁₆H₁₇N₅O₅
• 分子量: 359.341
• InChiKey: IXOCYFNFUHKMBH-UFEGPYSHSA-N

物化性质

• 沸点：
  589.0±50.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-amino-5-cyano-7-(5-deoxy-2,3-di-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 在 盐酸 、 乙醇 、 溶剂黄146 、 sodium nitrite 、 三氯氧磷 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 7.0h， 生成 6-amino-8-(5-deoxy-2,3-di-O-acetyl-β-D-ribofuranosyl)-4-methylpyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine
  参考文献：
  名称：

  Deoxy Sugar Analogues of Triciribine:  Correlation of Antiviral and Antiproliferative Activity with Intracellular Phosphorylation

  摘要：

  Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and antineoplastic activity at low micromolar or submicromolar concentrations. In an effort to improve and better understand this activity, we have conducted a structure-activity relationship study to explore requirements for the number of hydroxyl groups on the ribosyl moiety for biological activity. 2'-Deoxytriciribine (2'-dTCN), 3'-deoxytriciribine (3'-dTCN), 2',3'-epoxytriciribine (2',3'-epoxyTCN), 2',3'-dideoxy-2',3'-didehydrotriciribine (2',3'-d4TCN), and 2',3'-dideoxytriciribine (2',3'-ddTCN) were synthesized and evaluated for activity against human immunodeficiency virus (HIV-1), herpes simplex virus type 1 (HSV-1), and human cytomegalovirus (HCMV). Antiproliferative activity of the compounds also was tested in murine L1210 cells and three human tumor cell lines. All compounds were either less active than TCN and TCN-P or inactive at the highest concentration tested (100 mu M) in both antiviral and antiproliferative assays. Reverse-phase HPLC of extracts from uninfected cells treated with the deoxytriciribine analogues only detected the conversion of 3'-dTCN and 2',3'-ddTCN to their respective monophosphates. Therefore, either the deoxytriciribine analogues were not transported across the cell membrane or, more likely, they were not substrates for a nucleoside kinase or phosphotransferase. We have concluded that the hydroxyl groups on the ribosyl ring system of TCN and TCN-P must be intact in order to obtain significant antiviral and antineoplastic activity.

  DOI：

  10.1021/jm990205m
• 作为产物：
  描述：

  三-o-乙酰基-5-脱氧-d-呋喃核糖 在 10percent Pd/C 硫酸氢铵 、 氢气 、 三乙胺 、 六甲基二硅氮烷 作用下， 以 1,4-二氧六环 、 间二甲苯 为溶剂， 20.0 ℃ 、172.37 kPa 条件下， 反应 22.0h， 生成 4-amino-5-cyano-7-(5-deoxy-2,3-di-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis and Cytokine Modulation Properties of Pyrrolo[2,3-d]-4-pyrimidone Nucleosides

  摘要：

  A series of pyrrolo[2,3-d]pyrimidone nucleosides were synthesized and evaluated for their ability to enhance Type 2 cytokines and to suppress Type 1 cytokines in human T cells activated in vitro. Compounds 16b, 16c, 16d, 18c, and 19b induced substantial enhancement of IL-4 (a Type 2 cytokine) levels while three compounds (16b, 16c, and 16f) showed significant suppression of IFN gamma (a Type 1 cytokine) levels. The results revealed a strict structural requirement for the nucleoside-mediated enhancement of IL-4. Modifications of the ribofuranose moiety of the nucleosides either abolished or dramatically reduced the activity. Both the 5'-hydroxy and 5-carboxamidine are crucial for the activity. Of the few nucleoside analogues that demonstrated enhancement on Type 2 cytokine production, 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d]-4-pyrimidone-5-carboxamidine (16c) showed a dramatic enhancement (>200%) of IL-4 levels and a significant enhancement (36%) of IL-5 levels. Moreover, this compound showed substantial suppression of the Type 1 cytokines, IFN gamma (42%), IL-2 (54%), and TNF alpha (55%). Similarly, compound 16b showed a substantial enhancement of IL-4 (46%) and suppression of IL-2 (35%), IFN gamma (30%), and TNF alpha (26%). To our knowledge, these are the first nucleoside analogues that induce a Type 2 cytokine bias in T cells. The cytokine modulation property of 16c and 16b merits the therapeutic evaluation of these compounds in treating diseases in which immunopathology is associated with polarized Type 1 cytokine responses.

  DOI：

  10.1021/jm000035+