5-氟-6-碘尿苷 | 87818-06-2

• 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: 5-氟-6-碘尿苷
• 英文名称: 5-fluoro-6-iodouridine
• 英文别名: 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-fluoro-6-iodopyrimidine-2,4-dione
• CAS: 87818-06-2
• 化学式: C₉H₁₀FIN₂O₆
• 分子量: 388.091
• InChiKey: ATXHATZRJXXACM-UMMCILCDSA-N

物化性质

• 密度：
  2.31

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-氟-6-碘尿苷 在 吡啶 、 水 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 5-fluoro-6-iodouridine-5'-O-monophosphate
  参考文献：
  名称：

  Structure−Activity Relationships of Orotidine-5′-Monophosphate Decarboxylase Inhibitors as Anticancer Agents

  摘要：

  A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro, 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations.

  DOI：

  10.1021/jm801224t
• 作为产物：
  描述：

  5-氟-2',3'-异亚丙基尿苷 在 甲烷磺酸 、 碘 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 生成 5-氟-6-碘尿苷
  参考文献：
  名称：

  Synthesis and biological activities of 5-substituted 6-phenylthio and 6-iodouridines, a new class of antileukemic nucleosides.

  摘要：

  合成了一类新的5, 6-二取代尿苷，其中C-6位点被苯硫基或碘取代，通过相应5-取代的2', 3'-O-异丙烯基-5'-O-甲氧甲基尿苷的锂化及后续的电亲核反应进行合成。这些新合成的尿苷衍生物在培养中表现出对小鼠白血病L5178Y细胞的抗白血病活性。

  DOI：

  10.1248/cpb.31.2164

文献信息

• Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides
  作者：Magdalena Slusarczyk、Salvatore Ferla、Andrea Brancale、Christopher McGuigan

  DOI：10.1016/j.bmc.2017.11.037

  日期：2018.2

  family of thirteen phosphoramidate prodrugs (ProTides) of different 6-substituted-5-fluorouridine nucleoside analogues were synthesized and evaluated as potential anticancer agents. In addition, antiviral activity against Chikungunya (CHIKV) virus was evaluated using a cytopathic effect inhibition assay. Although a carboxypeptidase Y assay supported a putative mechanism of activation of ProTides built

  合成了新的十三种不同的6-取代的5-氟尿苷核苷类似物的氨基磷酸酯前药（ProTides）家族，并将其评估为潜在的抗癌药。另外，使用细胞病变效应抑制测定法评估了对基孔肯雅（CHIKV）病毒的抗病毒活性。尽管羧肽酶Y分析支持了建立在5-氟尿苷上的具有此类C6修饰的ProTides的推定机制，但Hint对接研究显示，Hint磷酸酰胺酶型酶的底物活性受到损害，这很可能是通过P引起氨基磷酸酯生物激活的原因。 -N键裂解和游离核苷5'-单磷酸酯传递。我们的观察结果可能会在一定程度上支持和解释体外的不良状况 一系列6-取代的5-氟尿嘧啶氨基磷酸酯（ProTides）普遍证明了其生物活性，并将为新型氨基磷酸酯前药的设计提供指导。
• ODCASE INHIBITORS FOR THE TREATMENT OF MALARIA
  申请人：Kotra Lakshmi P.

  公开号：US20090221524A1

  公开（公告）日：2009-09-03

  The present invention includes methods of treating or preventing malaria by administering an anti-malarial effective amount of 6-substituted uridine derivatives to a subject need thereof. The invention also includes new 6-substituted uridine derivatives for use as therapeutics, in particular to treat malaria.

  本发明涉及通过向需要治疗或预防疟疾的受体施用抗疟疾有效量的6-取代尿嘧啶衍生物来治疗或预防疟疾的方法。本发明还包括新的6-取代尿嘧啶衍生物，用于作为治疗剂，特别是用于治疗疟疾。
• Pyrimidine Derivatives As Anticancer Agents
  申请人：Kotra Lakshmi P.

  公开号：US20100056468A1

  公开（公告）日：2010-03-04

  The present invention includes methods of treating or preventing cancer by administering an effective amount of 6-substituted pyrimidine derivatives of the Formula I to a subject need thereof:

  本发明涉及通过向需要该治疗的受体施用公式I的6-取代嘧啶衍生物的有效量来治疗或预防癌症的方法：
• ODCASE INHIBITORS AS ANTI-VIRALS AND ANTIBIOTICS
  申请人：Kotra Lakshmi P.

  公开号：US20100087388A1

  公开（公告）日：2010-04-08

  The present invention includes the utility of anti-viral and/or antibacterial effective amounts of 6-substituted nucleoside derivatives of formula (I) (e.g. 6-iodouridine and 6-iodouridine monophosphate) in the treatment or prevention of viral infections (e.g. Flavivridae, Bunyaviridae, or Togaviridae, or viral infections of hepatitis C, hepatitis B, herpes, influenza, HIV, polio, Coxsackie A/B, rhino, small pox, Ebola, West Nile, or corona virus) and/or bacterial infections (e.g. H. pylori, S. Aureus, B. anthracis, Mycobacterial tuberculosis, M. leprae, M. avium, P. aueruginosa, Streptococcal species, and Pneumocystis carinii ).

  本发明涉及式（I）的6-取代核苷衍生物（例如6-碘尿嘧啶和6-碘尿苷酸单磷酸盐）的抗病毒和/或抗细菌有效量的实用性，用于治疗或预防病毒感染（例如黄病毒科、布尼亚病毒科、托加病毒科或丙型肝炎、乙型肝炎、疱疹、流感、艾滋病毒、脊髓灰质炎、柯萨奇A/B病毒、鼻病毒、天花、埃博拉、西尼罗河或冠状病毒）和/或细菌感染（例如幽门螺杆菌、金黄色葡萄球菌、炭疽杆菌、结核分枝杆菌、麻风分枝杆菌、非结核分枝杆菌、铜绿假单胞菌、链球菌属和肺孢子菌）。
• US8067391B2
  申请人：——

  公开号：US8067391B2

  公开（公告）日：2011-11-29