5'-脱氧丰加霉素 | 65562-55-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5'-脱氧丰加霉素
• 英文名称: 5'-deoxytoyocamycin
• 英文别名: 5'-doxytoyocamycin；4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 65562-55-2
• 化学式: C₁₂H₁₃N₅O₃
• 分子量: 275.267
• InChiKey: FONCIRHYMMLGTI-JJNLEZRASA-N

物化性质

• 沸点：
  644.3±55.0 °C(Predicted)
• 密度：
  1.78±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-脱氧丰加霉素 在 吡啶 、 溶剂黄146 、 sodium nitrite 、 三氯氧磷 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 10.0h， 生成 5-cyano-7-(5-deoxy-2,3-di-O-acetyl-β-D-ribofuranosyl)-4-(1-methylhydrazino)pyrrolo[2,3-d]pyrimidine
  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：

  4-氨基-5-氰基-7-(beta-d-呋喃核糖)吡咯并[2,3-d]嘧啶 在 六甲基磷酰三胺 、 氯化亚砜 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 5'-脱氧丰加霉素
  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

文献信息

• An Expeditious Total Synthesis of 5′-Deoxy-toyocamycin and 5′-Deoxysangivamycin
  作者：Xiangyou Dong、Jie Tang、Chen Hu、Jiang Bai、Haixin Ding、Qiang Xiao

  DOI：10.3390/molecules24040737

  日期：——

  In present paper, an expeditious total synthesis of naturally occurring 5′-deoxytoyocamycin and 5′-deoxysangivamycin was accomplished. Because of the introduction of a benzoyl group at N-6 of 4-amino-5-cyano-6-bromo-pyrrolo[2,3-d]pyrimidine, a Vorbrüggen glycosylation with 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose afforded a completely regioselective N-9 glycosylation product, which is unambiguously

  在本文中，完成了天然存在的 5'-脱氧丰霉素和 5'-脱氧桑吉霉素的快速全合成。由于在 4-amino-5-cyano-6-bromo-pyrrolo[2,3-d]pyrimidine 的 N-6 处引入了苯甲酰基，因此与 1,2,3-tri-O-乙酰基的 Vorbrüggen 糖基化-5-脱氧-β-D-呋喃核糖提供了完全区域选择性的 N-9 糖基化产物，X 射线衍射分析明确证实了这一点。所有涉及的中间体都通过各种光谱进行了很好的表征。
• 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
• 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。
• 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.
• PYRROLO(2,3-D)PYRIMIDINE NUCLEOSIDE ANALOGS
  申请人：Ribapharm, Inc.

  公开号：EP1363581A2

  公开（公告）日：2003-11-26