5'-O-tosyl-5-fluorouridine | 82207-41-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5'-O-tosyl-5-fluorouridine
• 英文别名: [(2R,3S,4R,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl 4-methylbenzenesulfonate
• CAS: 82207-41-8
• 化学式: C₁₆H₁₇FN₂O₈S
• 分子量: 416.384
• InChiKey: UFQHYYQCUVWWEM-RGCMKSIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-氟-2',3'-异亚丙基尿苷 在 吡啶 、 三氟乙酸 作用下， 反应 18.5h， 生成 5'-O-tosyl-5-fluorouridine
  参考文献：
  名称：

  Synthesis and biological activity of 5'-substituted 5-fluoropyrimidine nucleosides

  摘要：

  5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-deoxy-5'-substituted-5-fluorouridine (FUrd) derivatives in an effort to obtain compounds that might have improved substrate interactions compared to 1 and thus possibly be better prodrugs of FUra. Three derivatives, 5'-O-tosyl-FUrd (13), 5'-O-mesyl-FUrd (14), and 5'-deoxy-5'-bromo-FUrd (15), had cytostatic activity against L1210 and CCRF-CEM leukemic cells in culture superior to that of 1. In preliminary in vivo antitumor studies against L1210 leukemic cells in mice, 5'-deoxy-5'-chloro-FUrd (4), 5'-O-mesyl-FUrd (14), an 5'-deoxy-5'-fluoro-FUrd (18) gave percent increases in life span of 64, 58, and 58, respectively, compared to a value of 20 for compound 1.

  DOI：

  10.1021/jm00350a024

文献信息

• PROCESS FOR THE PREPARATION OF A DEOXYURIDINE DERIVATIVE
  申请人：PRO.BIO.SINT. S.r.l.

  公开号：EP0984976A1

  公开（公告）日：2000-03-15
• US5783689A
  申请人：——

  公开号：US5783689A

  公开（公告）日：1998-07-21
• [EN] PROCESS FOR THE PREPARATION OF A DEOXYURIDINE DERIVATIVE<br/>[FR] PROCEDE DE PREPARATION D'UN DERIVE DE DEOXYURIDINE
  申请人：PRO.BIO.SINT S.R.L.

  公开号：WO1998052960A1

  公开（公告）日：1998-11-26

  (EN) A process for the preparation of 5'-deoxy-5-fluorouridine, which comprises the transformation of 2',3'-O-isopropylidene-5-fluorouridine in the corresponding 5'-O-sulfonyl derivative, subsequent reaction with alkaline or earth-alkaline iodides and, after hydrolysis of the isopropylidene group, reduction of the 5'-deoxy-5'-iodo-5-fluorouridine thus obtained, is described.(FR) L'invention concerne un procédé de préparation de 5'-déoxy-fluorouridine, le procédé consistant à transformer 2',3'-O-isopropylidène-5-fluorouridine en un dérivé 5'-O-sulfonyle correspondant, puis à le mettre en réaction avec des iodures alcalins ou alcalinoterreux, et après hydrolyse du groupe isopropylidène, à réduire le 5'-déoxy-5'-iodo-5-fluorouridine ainsi obtenu.
• Synthesis and biological activity of 5'-substituted 5-fluoropyrimidine nucleosides
  作者：Sudhir Ajmera、Peter V. Danenberg

  DOI：10.1021/jm00350a024

  日期：1982.8

  5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-deoxy-5'-substituted-5-fluorouridine (FUrd) derivatives in an effort to obtain compounds that might have improved substrate interactions compared to 1 and thus possibly be better prodrugs of FUra. Three derivatives, 5'-O-tosyl-FUrd (13), 5'-O-mesyl-FUrd (14), and 5'-deoxy-5'-bromo-FUrd (15), had cytostatic activity against L1210 and CCRF-CEM leukemic cells in culture superior to that of 1. In preliminary in vivo antitumor studies against L1210 leukemic cells in mice, 5'-deoxy-5'-chloro-FUrd (4), 5'-O-mesyl-FUrd (14), an 5'-deoxy-5'-fluoro-FUrd (18) gave percent increases in life span of 64, 58, and 58, respectively, compared to a value of 20 for compound 1.