5-fluoro-6-ethyluridine-5'-O-monophosphate | 1039099-33-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 5-fluoro-6-ethyluridine-5'-O-monophosphate
• 英文别名: 5-fluoro-6-ethyl-UMP；{[(2R,3S,4R,5R)-5-(6-ethyl-5-fluoro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid；[(2R,3S,4R,5R)-5-(6-ethyl-5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 1039099-33-6
• 化学式: C₁₁H₁₆FN₂O₉P
• 分子量: 370.228
• InChiKey: JBBLQWFDKGRNST-VPCXQMTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 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-ethyluridine-5'-O-monophosphate 在 ammonium hydroxide 作用下， 以 水 为溶剂， 以222 mg的产率得到5-fluoro-6-ethyluridine-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-乙基尿苷 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-ethyluridine-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

• 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：
• [EN] PYRIMIDINE DERIVATIVES AS ANTICANCER AGENTS<br/>[FR] DÉRIVÉS DE PYRIMIDINE COMME AGENTS ANTI-CANCER
  申请人：UNIV HEALTH NETWORK

  公开号：WO2008083465A1

  公开（公告）日：2008-07-17

  [EN] 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:
  [FR] La présente invention comprend des procédés de traitement ou de prévention du cancer par administration d'une quantité efficace de dérivés de pyrimidine substitués en position 6, représentés par la Formule I, chez un sujet en ayant besoin.
• 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.