5-fluoro-6-iodouridine-5'-O-monophosphate | 933990-29-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 5-fluoro-6-iodouridine-5'-O-monophosphate
• 英文别名: 5-fluoro-6-iodo-UMP；[(2R,3S,4R,5R)-5-(5-fluoro-6-iodo-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 933990-29-5
• 化学式: C₉H₁₁FIN₂O₉P
• 分子量: 468.071
• InChiKey: NJSVPTGGTXIMLP-UMMCILCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-fluoro-6-iodouridine-5'-O-monophosphate 在 ammonium hydroxide 作用下， 以 水 为溶剂， 以202 mg的产率得到5-fluoro-6-iodouridine-5'-O-monophosphate diammonium salt
  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-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

文献信息

• 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。
• 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
• [EN] ODCASE INHIBITORS AS ANTI-VIRALS AND ANTIBIOTICS<br/>[FR] INHIBITEURS D'ODCASE EN TANT QU'ANTIVIRAUX ET ANTIBIOTIQUES
  申请人：KOTRA LAKSHMI P

  公开号：WO2007038860A2

  公开（公告）日：2007-04-12

  (EN) 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).(FR) La présente invention concerne l'utilité de quantités efficaces antivirales et/ou antibactériennes de dérivés de nucléoside substitués en 6 de formule (I) (par exemple, 6-iodouridine et 6-iodouridine monophosphate) dans le traitement ou la prévention d'infections virales (par exemple, Flavivridae, Bunyaviridae, ou Togaviridae, ou des infections virales de l'hépatite C, de l'hépatite B, de l'herpès, de la grippe, du VIH, de la polio, de Coxsackie A/B, de rhino, de la variole, d'Ebola, au virus du Nil occidental ou au virus corona) et/ou des infections bactériennes (par exemple, H. pylor S. Aureus, B. anthracis, la tuberculose mycobactérienne, M. leprae, M. avium, P. aueruginosa, des espèces de streptocoque, et Pneumocystis carinii).
• Structure−Activity Relationships of Orotidine-5′-Monophosphate Decarboxylase Inhibitors as Anticancer Agents
  作者：Angelica M. Bello、Danijela Konforte、Ewa Poduch、Caren Furlonger、Lianhu Wei、Yan Liu、Melissa Lewis、Emil F. Pai、Christopher J. Paige、Lakshmi P. Kotra

  DOI：10.1021/jm801224t

  日期：2009.3.26

  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.