1-(3'-azido-2',3'-dideoxy-5'-O-acetyl-β-D-ribofuranosyl)-5-methyl-4-(1,2,4-triazolyl)-pyrimidin-2-one | 87190-77-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(3'-azido-2',3'-dideoxy-5'-O-acetyl-β-D-ribofuranosyl)-5-methyl-4-(1,2,4-triazolyl)-pyrimidin-2-one
• 英文别名: 1-(5-O-Acetyl-3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-methyl-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone；ATAZT；5-methyl-4-(1,2,4-triazol-1-yl)-1-(5-O-acetyl-3-azido-2,3-dideoxy-β-D-ribofuranosyl)-pyrimidine-2(1H)-one；5-methyl-4-(1,2,4-triazol-1-yI)-1-(β-D-5'-O-acetyl-3'-azido-2',3'-dideoxyribo-furanosyl)-pyrimidine-2(1H)-on；[(2s,3s,5r)-3-Azido-5-[5-methyl-2-oxo-4-(1,2,4-triazol-1-yl)pyrimidin-1-yl]tetrahydrofuran-2-yl]methyl acetate；[(2S,3S,5R)-3-azido-5-[5-methyl-2-oxo-4-(1,2,4-triazol-1-yl)pyrimidin-1-yl]oxolan-2-yl]methyl acetate
• CAS: 87190-77-0
• 化学式: C₁₄H₁₆N₈O₄
• 分子量: 360.332
• InChiKey: MHODAINRPIQHQG-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(3'-azido-2',3'-dideoxy-5'-O-acetyl-β-D-ribofuranosyl)-5-methyl-4-(1,2,4-triazolyl)-pyrimidin-2-one 在 ammonium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以85%的产率得到3'-叠氮基-2',3'-二脱氧-5-甲基胞苷
  参考文献：
  名称：

  Synthesis and biological activity of various 3'-azido and 3'-amino analogs of 5-substituted pyrimidine deoxyribonucleosides

  摘要：

  Various new 5-substituted 3'-azido- and 3'-amino derivatives of 2'-deoxyuridine and 2'-deoxycytidine have been synthesized and biologically evaluated. Among these compounds, 3'-amino-2',3'-dideoxy-5-fluorouridine (3), 3'-amino-2',3'-dideoxycytidine (7a), and 3'-amino-2',3'-dideoxy-5-fluorocytidine (7c) were found to be the most active against murine L1210 and sarcoma 180 neoplastic cells in vitro, with an ED50 of 15 and 1 microM, 0.7 and 4 microM, and 10 and 1 microM, respectively. The 3'-azido derivatives, 2 and 6c, were less active in comparison with their 3'-amino counterparts. In addition, the 5-fluoro-3'-amino nucleosides, 3 and 7c, were tested against L1210 leukemia bearing CDF1 mice. Our preliminary findings indicate that compound 7c (6 X 200 mg/kg) was as active as the positive control, 5-fluorouracil (6 X 20 mg/kg), yielding a T/C X 100 of 146 and 129, respectively. However, 3 was found to be inactive in this experiment.

  DOI：

  10.1021/jm00366a006
• 作为产物：
  描述：

  齐多夫定 在 吡啶 、 三乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 1-(3'-azido-2',3'-dideoxy-5'-O-acetyl-β-D-ribofuranosyl)-5-methyl-4-(1,2,4-triazolyl)-pyrimidin-2-one
  参考文献：
  名称：

  N4-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine—New drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate)

  摘要：

  Amino-bisphosphonates (alendronate, pamidronate) were covalently linked in a three step synthesis, with protected and triazolylated derivatives of therapeutically used nucleoside analogs (5-FdU, araC, AZT) by substitution of their triazolyl residue. From the deprotected and chromatographically purified reaction mixtures N-4-[alkyl-(hydroxyphosphono) phosphonate]-cytidine combining two differently cytotoxic functions were obtained. This new family of bisphosphonates (BPs) contains as novelty an alkyl side chain with a cytotoxic nucleoside. The BPs moiety allows for a high binding to hydroxyapatite which is a prerequisite for bone targeting of the drugs. In vitro binding of 5-FdU-alendronate (5-FdU-ale) to hydroxyapatite showed a sixfold increased binding of these BPs as compared to 5-FdU.Exploratory cytotoxic properties of 5-FdU-ale were tested on a panel of human tumor cell lines resulting in growth inhibition ranging between 5% and 38%. The determination of IC50-concentrations of the conjugate in Lewis lung carcinoma and murine macrophages showed an incubation time dependent growth inhibition with higher sensitivity towards the tumor cells. We assume that the antimetabolite-BPs can be cleaved into different active metabolites that may exert cytotoxic and other therapeutic effects. However, the underlying mechanisms of these promising new antimetabolite-BPs conjugates remain to be evaluated in future experiments. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.015

文献信息

• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• Nucleoside and use thereof
  申请人：Burroughs Wellcome Co.

  公开号：US05041543A1

  公开（公告）日：1991-08-20

  A compound 1-(3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranoxyl)-5-methyl-2(1H)-pyr imidinone and its use in a method of generating (forming, providing) 3'-azido-3'-deoxythymidine (zidovudine sometimes referred to as AZT) in the body of an animal (a mammal such as human) by systemically administering 1-(3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl)-5-methyl-2(1H)-pyr iminone to said animal (mammal such as a human) is disclosed. AZT is approved and used for treating HIV infections, e.g., AIDS and ARC in humans and also has activity against gram-negative bacteria in animals.

  一种化合物1-(3-偶氮基-2,3-二脱氧-β-D-赤霉糖基)-5-甲基-2(1H)-嘧啶酮及其在通过系统给药1-(3-偶氮基-2,3-二脱氧-β-D-赤霉糖基)-5-甲基-2(1H)-嘧啶酮到动物（哺乳动物如人类）体内生成（形成，提供）3'-偶氮基-3'-脱氧胸苷（有时称为AZT）的方法中的应用被披露。AZT已经获批用于治疗人类的HIV感染，例如艾滋病和ARC，并且对动物的革兰氏阴性细菌也具有活性。
• Therapeutic nucleosides
  申请人：Burroughs Wellcome Co.

  公开号：US05064946A1

  公开（公告）日：1991-11-12

  Several novel 3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl derivatives of substituted pyrimidinones having antiretroviral, especially anti-AIDS, activity are described.

  本文介绍了几种新型的3-叠氮基-2,3-二去氧-β-D-鼠李糖-戊糖衍生物，这些衍生物是取代嘧啶酮的抗逆转录病毒，特别是抗艾滋病活性。
• Synthesis and anti-HIV activity of C4-modified pyrimidine nucleosides
  作者：Mark P Wallis、Naheed Mahmood、William Fraser

  DOI：10.1016/s0014-827x(98)00107-4

  日期：1999.1

  One-pot syntheses provided a series of triazole- and pentafluorophenyloxy-substituted pyrimidine nucleosides. Most of the compounds in the series displayed anti-HIV activities but none as potent as AZT 2. 1-(beta-D-Erythro-pentofuranosyl)-4-pentafluorophenyloxy-2(1H)-pyr imidinone 14 was the most potent and the most selective compound in the series with EC50 = 1.6 microM.
• J. Med. Chem. 1983, 26, 1691-1696
  作者：

  DOI：——

  日期：——