[(2R,3R,4R,5R)-4-acetyloxy-5-(4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-2-methyloxolan-3-yl] acetate | 288388-08-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2R,3R,4R,5R)-4-acetyloxy-5-(4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-2-methyloxolan-3-yl] acetate
• CAS: 288388-08-9
• 化学式: C₁₆H₁₆BrN₅O₅
• 分子量: 438.238
• InChiKey: ZSKBSTXHVYJMKG-YGCSDREMSA-N

物化性质

• 沸点：
  635.6±55.0 °C(Predicted)
• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  27
• 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：

  [(2R,3R,4R,5R)-4-acetyloxy-5-(4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-2-methyloxolan-3-yl] acetate 在 10percent Pd/C 氨 、 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0~130.0 ℃ 、172.37 kPa 条件下， 反应 5.5h， 生成 5'-脱氧丰加霉素
  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+
• 作为产物：
  描述：

  三-o-乙酰基-5-脱氧-d-呋喃核糖 、 4-氨基-6-溴-7H-吡咯并[2,3-d]嘧啶-5-甲腈 在 硫酸氢铵 、 六甲基二硅氮烷 、 三氟甲磺酸三甲基硅酯 作用下， 以 间二甲苯 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 以51%的产率得到[(2R,3R,4R,5R)-4-acetyloxy-5-(4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-2-methyloxolan-3-yl] acetate
  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+

文献信息

• Pyrrolo[2,3-d]pyrimidine nucleoside analogs
  申请人：——

  公开号：US20020035077A1

  公开（公告）日：2002-03-21

  Compositions and methods for pyrrolo[2,3-d]pyrimidine nucleoside analogs having substituents at the C4′ and C5′ positions of the ribofuranose moiety are presented. Contemplated compositions exhibit, among other things, anti-cancer and immunomodulating effects at reduced cytotoxicity.

  本发明提供了在核糖苷骨架的C4'和C5'位置具有取代基的吡咯[2,3-d]嘧啶核苷类似物的组合物和方法。考虑到的组合物在减少细胞毒性的情况下表现出抗癌和免疫调节等效果。
• US6831069B2
  申请人：——

  公开号：US6831069B2

  公开（公告）日：2004-12-14