4-amino-5-cyano-7-β-D-arabinofuranosylpyrrolo(2,3-d)pyrimidine | 90813-71-1

• 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: 4-amino-5-cyano-7-β-D-arabinofuranosylpyrrolo(2,3-d)pyrimidine
• 英文别名: arabinotoyocamycin；ara-toyocamycin；toyocamycin；4-Amino-7-beta-D-arabinofuranosyl-7H-pyrrolo(2,3-d)pyrimidine-5-carbonitrile；4-amino-7-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 90813-71-1
• 化学式: C₁₂H₁₃N₅O₄
• 分子量: 291.266
• InChiKey: XOKJUSAYZUAMGJ-QRKAXHLRSA-N

物化性质

• 沸点：
  721.1±60.0 °C(Predicted)
• 密度：
  1.91±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 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：
  150
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-5-cyano-7-β-D-arabinofuranosylpyrrolo(2,3-d)pyrimidine 在 溶剂黄146 、 sodium nitrite 作用下， 反应 1.0h， 以79%的产率得到5-cyano-7-(β-D-arabinofuranosyl)pyrrolo[2,3-d]-4-pyrimidone
  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：

  4-amino-7-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)pyrrolo<2,3-d>pyrimidine-5-carbonitrile 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到4-amino-5-cyano-7-β-D-arabinofuranosylpyrrolo(2,3-d)pyrimidine
  参考文献：
  名称：

  结构上与抗生素丰卡霉素和桑格霉素有关的5-取代-7-β-D-阿拉伯呋喃糖基吡咯并[2,3- d ]嘧啶的简便合成

  摘要：

  由2-乙氧基亚甲基氨基-5-制备的4-氨基-7-（2,3,5-三-O-苄基-β-D-阿拉伯呋喃糖基）吡咯并[2,3 - d ]嘧啶-5-腈（6a）用三氯化硼将溴吡咯-3，4-二碳腈（4）脱苄基，得到ara- totocamycin（6b）。6b的进一步官能团转化提供了通往4-氨基-7-β-D-阿拉伯呋喃糖基吡咯并[2,3 - d ]嘧啶-5-硫代羧酰胺（ara - thiosangivamycin，7a）以及相应的5-羧酰胺肟8a和5的途径。-羧box8b衍生物。未保护的7a的磷酸化三氯氧磷给ARA -thiosangivamycin 5'-单磷酸（7B）。2'- ø乙酰基ARA -thiosangivamycin（10B制备通过乙酰化前药）9A，接着脱保护吨酸性条件下丁基二组，而不用酰基迁移。

  DOI：

  10.1002/jhet.5570250366

文献信息

• 2' And 3'-ketonucleosides and their arabino and xylo reduction products
  作者：Fritz Hansske、Danuta Madej、Morris J. Robins

  DOI：10.1016/0040-4020(84)85111-x

  日期：1984.1

  A number of 2',5'- or 3',5'-diprotected ribonucleosides and 5'-protected 2'- or 3'-deoxy-β-D-erythro-pentofuranosyl nucleosides have been oxidized to the corresponding 3' or 2'-ketonucleoside derivatives using chromium trioxide/pyridine/acetic anhydride or dimethyl sulfoxide/ acetic anhydride. Reduction of the carbonyl functions with sodium borohydride gave the inverted arabino, xylo, or deoxy-threo

  许多2'，5'-或3'，5'-双保护核糖核苷和5'-保护的2'-或3'-脱氧-β-D-赤型-戊呋喃糖基核苷已被氧化为相应的3'或2使用三氧化铬/吡啶/乙酸酐或二甲基亚砜/乙酸酐的'-酮核苷衍生物。用硼氢化钠还原羰基官能团，可以通过在糖环的受阻较少的α面上进行攻击，使倒位的阿拉伯糖，木糖或脱氧苏糖异构体成为主要产物。通过证明已经发生了原始羟基的完全氧化，使用硼氢化氘化钠的平行还原证实了差向异构体比率。氘标记还有助于进行NMR 频谱分配。
• Synthesis and Evaluation of Certain Thiosangivamycin Analogs as Potential Inhibitors of Cell Proliferation and Human Cytomegalovirus
  作者：Steven H. Krawczyk、Thomas E. Renau、M. Reza Nassiri、Allison C. Westerman、Linda L. Wotring、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm00020a027

  日期：1995.9

  7-substituted 4-aminopyrrolo[2,3-d]pyrimidines related to the nucleosides toyocamycin and thiosangivamycin were prepared and tested for their activity against human cytomegalovirus (HCMV). The nucleosides 2'-deoxytoyocamycin (1), xylo-toyocamycin (2), 3'-deoxytoyocamycin (3), 2',3'-dideoxy-2',3'-didehydrotoyocamycin (4), 2',3'-dideoxytoyocamycin (5), ara-toyocamycin (6), 2'-deoxy-2'-amino-ara-toyocamycin

  制备了一系列与核苷丰卡霉素和硫代桑奇霉素有关的7-取代的4-氨基吡咯并[2,3-d]嘧啶，并测试了它们对人巨细胞病毒（HCMV）的活性。核苷2'-脱氧代代霉素（1），木糖-代代霉素（2），3'-脱氧代代霉素（3），2'，3'-脱氧代代-2'，3'-脱氢代代代霉素（4），2'，3'-用就地生成的硫化氢处理二脱氧代代霉素（5），阿拉伯代代霉素（6），2'-脱氧-2'-氨基-代代代霉素（7）和5'-脱氧代代霉素（8）。 thiosangivamycin类似物（9-16）。通过修改文献方法合成氰基衍生物1-8。所有的硫代酰胺衍生物（9-16）均具有抗HCMV的活性，IC50为0.5至6 microM。大多数还对1型单纯疱疹病毒（HSV-1）具有活性，但浓度较高。在两种人类细胞系中，抗病毒活性并未与细胞毒性完全分开。糖基上修饰的位置强烈影响抗增殖活性。与在2'，5'或2'，3'位置进行修饰的木糖基和
• 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.
• A convenient synthesis of 5-substituted-7-β-D-arabinofuranosylpyrrolo[2,3-<i>d</i>]pyrimidines structurally related to the antibiotics toyocamycin and sangivamycin
  作者：Kandasamy Ramasamy、Roland K. Robins、Ganapathi R. Revankar

  DOI：10.1002/jhet.5570250366

  日期：1988.5

  4-Amino-7-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carbonitrile (6a), prepared from 2-ethoxymethyleneamino-5-bromopyrrole-3,4-dicarbonitrile (4), was debenzylated with boron trichloride to give ara-toyocamycin (6b). Further functional group transformation of 6b provided a route to 4-amino-7-β-D-arabinofuranosylpyrrolo[2,3-d]pyrimidine-5-thiocarboxamide (ara-thiosangivamycin

  由2-乙氧基亚甲基氨基-5-制备的4-氨基-7-（2,3,5-三-O-苄基-β-D-阿拉伯呋喃糖基）吡咯并[2,3 - d ]嘧啶-5-腈（6a）用三氯化硼将溴吡咯-3，4-二碳腈（4）脱苄基，得到ara- totocamycin（6b）。6b的进一步官能团转化提供了通往4-氨基-7-β-D-阿拉伯呋喃糖基吡咯并[2,3 - d ]嘧啶-5-硫代羧酰胺（ara - thiosangivamycin，7a）以及相应的5-羧酰胺肟8a和5的途径。-羧box8b衍生物。未保护的7a的磷酸化三氯氧磷给ARA -thiosangivamycin 5'-单磷酸（7B）。2'- ø乙酰基ARA -thiosangivamycin（10B制备通过乙酰化前药）9A，接着脱保护吨酸性条件下丁基二组，而不用酰基迁移。