1-(5-磷酰-beta-D-阿拉伯呋喃糖基)-5-氟尿嘧啶 | 17124-23-1

• 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
• 中文名称: 1-(5-磷酰-beta-D-阿拉伯呋喃糖基)-5-氟尿嘧啶
• 中文别名: 1-(5-二氧磷基-β-D-呋喃阿拉伯糖基)-5-氟尿苷
• 英文名称: Phosphoric acid mono-[(2R,3S,4S,5R)-5-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl] ester
• 英文别名: 1-(5-Phospho-beta-D-arabinofuranosyl)-5-fluorouracil；[(2R,3S,4S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 17124-23-1
• 化学式: C₉H₁₂FN₂O₉P
• 分子量: 342.174
• InChiKey: RNBMPPYRHNWTMA-MNCSTQPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  22
• 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

• 作为产物：
  描述：

  Phosphoric acid mono-((2R,3R,3aS,9aR)-7-fluoro-3-hydroxy-6-oxo-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-2-ylmethyl) ester 在 水 作用下， 反应 3.0h， 生成 1-(5-磷酰-beta-D-阿拉伯呋喃糖基)-5-氟尿嘧啶
  参考文献：
  名称：

  Interaction of 1-(5-phospho-.beta.-D-arabinofuranosyl)-5-substituted-uracils with thymidylate synthetase: mechanism-based inhibition by 1-(5-phospho-.beta.-D-arabinofurosyl)-5-fluorouracil

  摘要：

  A number of 1-(5-phospho-beta-D-arabinosyl)-5-substituted-uracils (ara-UMP's) have been examined as inhibitors of dTMP synthetase. As reversible inhibitors, all were substantially less potent than their 2'-deoxyribosyl counterparts. In the presence of 5,10-methylenetetrahydrofolate (CH2-H4folate), ara-FUMP caused a first-order, time-dependent inactivation of the enzyme. At 0 degrees C, kinetic studies indicated a reversible Kd of 3.6 micro M for the ara-FUMP-CH2-H4folate complex, and k = 0.22 min-1 for the subsequent inactivation. Spectral studies of the complex and its behavior toward protein denaturants demonstrate that its structure and stoichiometry are directly analogous to those which have previously been described for FdUMP. The significance of this finding with regard to prodrugs of ara-FU and the potential of ara-FU as a chemotherapeutic agent are discussed.

  DOI：

  10.1021/jm00142a008

文献信息

• Interaction of 1-(5-phospho-.beta.-D-arabinofuranosyl)-5-substituted-uracils with thymidylate synthetase: mechanism-based inhibition by 1-(5-phospho-.beta.-D-arabinofurosyl)-5-fluorouracil
  作者：Chikao Nakayama、Yusuke Wataya、Daniel V. Santi、Mineo Saneyoshi、Tohru Ueda

  DOI：10.1021/jm00142a008

  日期：1981.10

  A number of 1-(5-phospho-beta-D-arabinosyl)-5-substituted-uracils (ara-UMP's) have been examined as inhibitors of dTMP synthetase. As reversible inhibitors, all were substantially less potent than their 2'-deoxyribosyl counterparts. In the presence of 5,10-methylenetetrahydrofolate (CH2-H4folate), ara-FUMP caused a first-order, time-dependent inactivation of the enzyme. At 0 degrees C, kinetic studies indicated a reversible Kd of 3.6 micro M for the ara-FUMP-CH2-H4folate complex, and k = 0.22 min-1 for the subsequent inactivation. Spectral studies of the complex and its behavior toward protein denaturants demonstrate that its structure and stoichiometry are directly analogous to those which have previously been described for FdUMP. The significance of this finding with regard to prodrugs of ara-FU and the potential of ara-FU as a chemotherapeutic agent are discussed.