4-Amino-5-cyano-7-(2,3-dideoxy-β-D-glycero-pentofuranosyl)pyrrolo<2,3-d>pyrimidine | 115044-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-Amino-5-cyano-7-(2,3-dideoxy-β-D-glycero-pentofuranosyl)pyrrolo<2,3-d>pyrimidine
• 英文别名: 2',3'-dideoxytoyocamycin；7H-Pyrrolo(2,3-d)pyrimidine-5-carbonitrile, 4-amino-7-((2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furanyl)-；4-amino-7-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 115044-81-0
• 化学式: C₁₂H₁₃N₅O₂
• 分子量: 259.268
• InChiKey: ZQWLOVYPSSKGMA-DTWKUNHWSA-N

物化性质

• 熔点：
  197-197.5 °C
• 沸点：
  591.4±50.0 °C(Predicted)
• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 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：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-Amino-5-cyano-7-(2,3-dideoxy-β-D-glycero-pentofuranosyl)pyrrolo<2,3-d>pyrimidine 在 盐酸羟胺 、 potassium carbonate 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 7-(2,3-dideoxy-β-D-ribofuranosyl)pyrrolo[2,3-d]-4-pyrimidone-5-carboxamidoxime
  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-氨基-5-氰基-7-(beta-d-呋喃核糖)吡咯并[2,3-d]嘧啶 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 19.0~22.0 ℃ 、68.94 kPa 条件下， 反应 5.0h， 生成 4-Amino-5-cyano-7-(2,3-dideoxy-β-D-glycero-pentofuranosyl)pyrrolo<2,3-d>pyrimidine
  参考文献：
  名称：

  Nucleic Acid-Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2',3'-Anhydro, 2'(and 3')-Deoxy, 2',3'-Didehydro-2',3'-dideoxy, and 2',3'-Dideoxynucleoside Analogs

  摘要：

  Treatment of purine, pyrimidine, and modified purine (antibiotic) ribonucleosides with 2-acetoxy-2-methylpropanoyl (alpha-acetoxyisobutyryl) bromide in acetonitrile gave mixtures of 2',3'-bromohydrin acetates with different O5' substituents. Significant amounts of 5'-unprotected (hydroxyl) bromo acetates were obtained in some cases, and formation of 2',3'-O-isopropylidene derivatives as minor byproducts was detected for the first time. Acid-catalyzed nucleophilic displacement of chloride by bromide occurred with 2-amino-6-chloropurine riboside, but no substitution of fluoride by bromide was detected with 6-amino-2-fluoropurine riboside. Treatment of the trans bromo acetate mixtures obtained from purine-type nucleosides with Dowex 1 x 2 (OH-) in methanol gave the 2',3'-anhydro (ribo epoxide) compounds. Radical-mediated hydrogenolytic debromination and deprotection gave 2'- and 3'-deoxynucleosides. Treatment of the bromo acetate mixtures with zinc-copper couple or acetic acid-activated zinc effected reductive elimination, and deprotection gave 2',3'-didehydro-2',3'-dideoxy compounds which were hydrogenated to give 2',3'-dideoxynucleosides. A number of these analogues have potent inhibitory activity against AIDS and hepatitis B viruses. New C-13 NMR data for several types of unsaturated-sugar nucleosides are tabulated. These procedures are directly applicable for the preparation of L-didehydro-dideoxy and L-dideoxy nucleoside analogues.

  DOI：

  10.1021/jo00129a034

文献信息

• 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
• KRAWCZYK, STEVEN H.;TOWNSEND, LEROY B., NUCLEOSIDES AND NUCLEOTIDES, 8,(1989) N, C. 97-115
  作者：KRAWCZYK, STEVEN H.、TOWNSEND, LEROY B.

  DOI：——

  日期：——
• US7202224B2
  申请人：——

  公开号：US7202224B2

  公开（公告）日：2007-04-10
• Nucleic Acid-Related Compounds. 88. Efficient Conversions of Ribonucleosides into Their 2',3'-Anhydro, 2'(and 3')-Deoxy, 2',3'-Didehydro-2',3'-dideoxy, and 2',3'-Dideoxynucleoside Analogs
  作者：Morris J. Robins、John S. Wilson、Danuta Madej、Nicholas H. Low、Fritz Hansske、Stanislaw F. Wnuk

  DOI：10.1021/jo00129a034

  日期：1995.12

  Treatment of purine, pyrimidine, and modified purine (antibiotic) ribonucleosides with 2-acetoxy-2-methylpropanoyl (alpha-acetoxyisobutyryl) bromide in acetonitrile gave mixtures of 2',3'-bromohydrin acetates with different O5' substituents. Significant amounts of 5'-unprotected (hydroxyl) bromo acetates were obtained in some cases, and formation of 2',3'-O-isopropylidene derivatives as minor byproducts was detected for the first time. Acid-catalyzed nucleophilic displacement of chloride by bromide occurred with 2-amino-6-chloropurine riboside, but no substitution of fluoride by bromide was detected with 6-amino-2-fluoropurine riboside. Treatment of the trans bromo acetate mixtures obtained from purine-type nucleosides with Dowex 1 x 2 (OH-) in methanol gave the 2',3'-anhydro (ribo epoxide) compounds. Radical-mediated hydrogenolytic debromination and deprotection gave 2'- and 3'-deoxynucleosides. Treatment of the bromo acetate mixtures with zinc-copper couple or acetic acid-activated zinc effected reductive elimination, and deprotection gave 2',3'-didehydro-2',3'-dideoxy compounds which were hydrogenated to give 2',3'-dideoxynucleosides. A number of these analogues have potent inhibitory activity against AIDS and hepatitis B viruses. New C-13 NMR data for several types of unsaturated-sugar nucleosides are tabulated. These procedures are directly applicable for the preparation of L-didehydro-dideoxy and L-dideoxy nucleoside analogues.
• 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.