jaspamycin | 22242-96-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: jaspamycin
• 英文别名: Jaspamycin；7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-oxo-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 22242-96-2
• 化学式: C₁₂H₁₂N₄O₅
• 分子量: 292.251
• InChiKey: SKDKFLFSBDYEDO-WOUKDFQISA-N

物化性质

• 沸点：
  724.3±70.0 °C(Predicted)
• 密度：
  1.91±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：41.67 mg/mL（142.58 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  7

制备方法与用途

生物活性 Jaspamycin (7-CN-7-C-Ino) 是一种有效的 PKA 激活剂，在 Trypanosoma brucei 中与其 R 位点 (PKAR) 结合，EC50 和 Kd 值分别为 6.5 nM 和 8 nM。Jaspamycin (7-CN-7-C-Ino) 不结合纯化的人 PKARIα，并具有抗寄生虫活性。

靶点

• Trypanosoma brucei PKA 环化酶全酶：8 nM (Kd)
• Trypanosoma brucei PKAR(199-499)：6.5 nM (EC50)

反应信息

• 作为反应物：
  描述：

  jaspamycin 在 镍 氢气 、 羟胺 作用下， 以 乙醇 为溶剂， 生成 7-(β-D-ribofuranosyl)pyrrolo[2,3-d]-4-pyrimidone-5-carboxamidine
  参考文献：
  名称：

  Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents

  摘要：

  Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5-carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good activity and selectivity. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2006.07.003
• 作为产物：
  描述：

  4-氨基-5-氰基-7-(beta-d-呋喃核糖)吡咯并[2,3-d]嘧啶 在 水 、 溶剂黄146 、 sodium nitrite 作用下， 反应 1.0h， 以84%的产率得到jaspamycin
  参考文献：
  名称：

  Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents

  摘要：

  Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5-carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good activity and selectivity. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2006.07.003

文献信息

• 一种贾斯帕霉素的合成方法
  申请人：康化（上海）新药研发有限公司

  公开号：CN112851719A

  公开（公告）日：2021-05-28

  本发明涉及一种贾斯帕霉素的合成方法。主要解决目前合成方法步骤长，成本高的技术问题。本发明合成步骤：4‑氯‑5‑碘‑7H‑吡咯并[2,3‑d]嘧啶和1‑乙酰基‑2,3,5‑三苯甲酰氧基‑1‑beta‑D‑呋喃核糖在N，O‑双（三甲基甲硅烷基）乙酰胺和三氟甲磺酸三甲基硅酯的作用下生成化合物1，产物打浆提纯；化合物1与甲醇钠在甲醇里反应，得到化合物2，无需提纯；化合物2在氢氧化钠水溶液里加热反应生成化合物3，产物打浆提纯；化合物3与氰化亚铜在吡啶里加热反应，所得粗品打浆，重结晶得到目标产物。
• Synthesis and Cytokine Modulation Properties of Pyrrolo[2,3-<i>d</i>]-4-pyrimidone Nucleosides
  作者：Guangyi Wang、Robert C. Tam、Esmir Gunic、Jinfa Du、Josie Bard、Bharati Pai

  DOI：10.1021/jm000035+

  日期：2000.6.1

  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.
• Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents
  作者：Chamakura V.N.S. Varaprasad、Kanda S. Ramasamy、Jean-Luc Girardet、Esmir Gunic、Vicky Lai、Weidong Zhong、Haoyun An、Zhi Hong

  DOI：10.1016/j.bioorg.2006.07.003

  日期：2007.2

  Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5-carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good activity and selectivity. (c) 2006 Elsevier Inc. All rights reserved.