3'-叠氮基-2',3'-二脱氧-5-碘尿苷 | 85236-92-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 3'-叠氮基-2',3'-二脱氧-5-碘尿苷
• 中文别名: 溴化3-(羧基甲基)-2-甲基苯并噻唑正离子
• 英文名称: 1-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-iodouracil
• 英文别名: 3'-azido-2',3'-dideoxy-5-iodouridine；5-iodo-3'-azido-2',3'-dideoxyuridine；1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione
• CAS: 85236-92-6
• 化学式: C₉H₁₀IN₅O₄
• 分子量: 379.114
• InChiKey: RKFULXUNGOGTPS-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3'-叠氮基-2',3'-二脱氧-5-碘尿苷 在 吡啶 、 铜 、 溶剂黄146 作用下， 反应 5.25h， 生成 3'-azido-2',3'-dideoxy-5-(trifluoromethyl)uridine
  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：

  Navuridine 在 acetic buffer 、 mercury(II) diacetate 、 碘 作用下， 生成 3'-叠氮基-2',3'-二脱氧-5-碘尿苷
  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

文献信息

• 3'-Amino-2',3'-dideoxyribonucleosides of some pyrimidines: synthesis and biological activities
  作者：Thomas A. Krenitsky、G. Andrew Freeman、Sammy R. Shaver、Lowrie M. Beacham、Stuart Hurlbert、Naomi K. Cohn、Lynn P. Elwell、John W. T. Selway

  DOI：10.1021/jm00360a019

  日期：1983.6

  the catalyst. 3'-Amino-2',3'-dideoxycytidine (7) was synthesized by amination of the 3'-azido precursor of 3'-amino-2',3'-dideoxyuridine. The biological activity of 3'-amino-2',3'-dideoxy-5-fluorouridine (6) was notable among this group of aminonucleosides. It had an ED50 of 10 microM against adenovirus and was not appreciably cytotoxic to mammalian cells in culture. It also had activity against some

  胸腺嘧啶，尿嘧啶和5-碘尿嘧啶的3'-氨基-2'，3'-二脱氧核糖核苷（1-3）是通过相应的2'-脱氧核糖核苷通过threo-3'-chloro和erythro-3'-合成的叠氮基衍生物。以3'-氨基-2'，3'-二脱氧胸苷为氨基戊糖基供体，以胸苷磷酸化酶（EC 2.4.2.4）为酶促合成了5-溴尿嘧啶，5-氯尿嘧啶和5-氟尿嘧啶（4-6）的相应氨基核苷催化剂。通过氨基化3′-氨基-2′，3′-二脱氧尿苷的3′-叠氮基前体合成3′-氨基-2′，3′-二脱氧胞苷（7）。在这组氨基核苷中，3'-氨基-2'，3'-二脱氧-5-氟尿苷的生物活性显着（6）。它对腺病毒的ED50为10 microM，对培养的哺乳动物细胞没有明显的细胞毒性。它也对某些革兰氏阳性细菌有活性，但对多种革兰氏阴性细菌没有活性。其他氨基核苷（1-5和7）缺乏或表现出弱的抗病毒和抗菌活性。该组中唯一对培养的哺乳动物细胞有明显毒性
• Synthesis and antiviral activity of several 2,5'-anhydro analogs of 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2',3'-dideoxyuridine (AZU), 3'-azido-2',3'-dideoxy-5-halouridines, and 3'-deoxythymidine against human immunodeficiency virus (HIV-1) and Rauscher-Murine leukemia virus (R-MuLV)
  作者：Tai Shun Lin、Zhi Yi Shen、E. Michael August、Vera Brankovan、Hyekyung Yang、Ismail Ghazzouli、William H. Prusoff

  DOI：10.1021/jm00128a034

  日期：1989.8

  Several 2,5'-anhydro analogues of 3'-azido-3'-deoxythymidine (AZT), 3'-azido-2'3'-dideoxyuridine (AZU), 3'-azido-2'3'-dideoxy-5-bromouridine, 3'-azido-2',3'-dideoxy-5-iodouridine, and 3'-deoxythymidine and the 3'-azido derivative of 5-methyl-2'-deoxyisocytidine have been synthesized for evaluation as potential anti-HIV (human immunodeficiency virus) agents. These 2,5'-anhydro derivatives, compounds

  3'-叠氮基-3'-脱氧胸苷（AZT），3'-叠氮基-2'3'-二脱氧尿苷（AZU），3'-叠氮基-2'3'-二脱氧-5的几个2,5'-脱水类似物已经合成了-溴尿苷，3'-叠氮基-2'，3'-二脱氧基-5-碘尿苷和3'-脱氧胸苷以及5-甲基-2'-脱氧异胞苷的3'-叠氮基衍生物，作为潜在的抗- HIV（人类免疫缺陷病毒）制剂。这些2,5'-脱水衍生物，化合物13-17，显示出显着的抗HIV-1活性，IC50值分别为0.56、4.95、26.5、27.1和48 microM。与母体化合物AZT和AZU相比，各自的2,5'-脱水类似物化合物13和14的活性略低。AZT具有TCID50为29 microM的细胞毒性，而AZT的2,5'-脱水衍生物化合物13的毒性 降低到TCID50值大于100 microM。5-甲基-2'-脱氧异胞苷的2,5'-脱水类似物也显示出抗HIV-1活性，IC50值为12
• Novel fluorophosphonate nucleotide derivatives
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0339161A1

  公开（公告）日：1989-11-02

  This invention relates to fluoromethylphosphonate derivatives of certain nucleosides, to methods for their preparation and to their use as antiviral and antitumoral agents.

  这项发明涉及某些核苷类化合物的氟甲基磷酸酯衍生物，涉及它们的制备方法以及它们作为抗病毒和抗肿瘤药物的用途。
• Investigation of C-5 alkynyl (alkynyloxy or hydroxymethyl) and/or N-3 propynyl substituted pyrimidine nucleoside analogs as a new class of antimicrobial agents
  作者：Saurabh Garg、Neeraj Shakya、Naveen C. Srivastav、Babita Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1016/j.bmc.2016.09.008

  日期：2016.11

  infections and the emergence of drug-resistant strains urgently require a new class of agents that are distinct than current therapies. A group of 5-ethynyl (6–10), 5-(2-propynyloxy) (16, 18, 20, 22, 24), 5-(2-propynyloxy)-3-N-(2-propynyl) (17, 19, 21, 23, 25) and 5-hydroxymethyl-3-N-(2-propynyl) (30–33) derivatives of pyrimidine nucleosides were synthesized and evaluated against mycobacteria [Mycobacterium

  分支杆菌感染的复发和耐药菌株的出现迫切需要一类不同于当前疗法的新型药物。A组5-乙炔基（的6 - 10），5-（2-丙炔氧基）（16，18，20，22，24），5-（2-丙炔氧基）-3- ñ - （2-丙炔基）（17，19，21，23，25）和5-羟甲基-3- ñ - （2-丙炔基）（30 - 33）的嘧啶核苷衍生物的合成和对分枝杆菌[评价结核分枝杆菌（Mtb），牛分枝杆菌（BCG）和鸟分枝杆菌），革兰氏阳性菌（金黄色葡萄球菌和粪肠球菌）和革兰氏阴性菌（大肠杆菌，鼠伤寒沙门氏菌和铜绿假单胞菌与单独的药物合用）体外测定。尽管几种化合物在较高浓度下对Mtb，牛分枝杆菌，金黄色葡萄球菌和粪肠球菌均表现出明显的抑制活性。，它们在较低的浓度下与抗结核药异烟肼和利福平以及抗菌药庆大霉素具有出乎意料的协同作用和加性相互作用。还发现了活性类似物在感染了H37Ra的人单核细胞系中抑制细胞内Mtb。5-羟甲基-3-口服给药ñ
• Pyridinone Diketo Acids: Inhibitors of HIV Replication in Combination Therapy
  申请人：Nair Vasu

  公开号：US20100092427A1

  公开（公告）日：2010-04-15

  A new class of diketo acids constructed on pyridinone scaffolds, designed as inhibitors of HTV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described. Compounds of the present application include those of formula I and include tautomers, regioisomers, geometric isomers, and pharmaceutically acceptable salts thereof, wherein the pyridinone scaffold and R groups are as otherwise defined in the specification. These are combined, with any number of typical other anti-HIV agents (including other integrase-based anti-HIV agents) and other combination therapeutic agents described herein, to provide an effective treatment modality for HIV infections, including AIDS and ARC.

  本文描述了一类新型的二酮酸，构建在吡啶酮支架上，设计用于通过抑制HIV整合酶来抑制HIV复制。这些化合物可用于预防或治疗HIV感染以及治疗AIDS和ARC，可以作为化合物本身或与药物载体结合使用，或与其他抗病毒药物、免疫调节剂、抗生素、疫苗和其他治疗剂联合使用，尤其是其他抗HIV化合物（包括其他抗HIV整合酶剂），以形成联合抗HIV药物组合。本申请的化合物包括公式I中的化合物和其中的互变异构体、区域异构体、几何异构体和其药学上可接受的盐，其中吡啶酮支架和R基在规范中另有定义。这些化合物与任意数量的典型其他抗HIV药物（包括其他基于整合酶的抗HIV药物）和其他联合治疗剂联合使用，提供了一种有效的治疗HIV感染的治疗模式，包括AIDS和ARC的治疗方法。