5-fluoro-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)uridine | 82276-89-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-fluoro-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)uridine
• 英文别名: 5-fluoro-2',3'-O-isopropylidene-5'-O-p-toluenesulfonyluridine；5'-O-tosyl-2',3'-O-isopropylidene-5-fluorouridine；2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)-5-fluorouridine；[(3aR,4R,6R,6aR)-4-(5-fluoro-2,4-dioxopyrimidin-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 4-methylbenzenesulfonate
• CAS: 82276-89-9
• 化学式: C₁₉H₂₁FN₂O₈S
• 分子量: 456.449
• InChiKey: XOOWBZXPHUYMAB-KCYZZUKISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-fluoro-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)uridine 生成 5'-deoxy-5-fluoro-2',3'-O-isopropylidene-5'-methyluridine
  参考文献：
  名称：

  HAYAKAWA, HIROYUKI;ASHIZAWA, HIROSHI;TANAKA, HIROMICHI;MIYASAKA, TADASHI, CHEM. AND PHARM. BULL., 38,(1990) N, C. 355-360

  摘要：

  DOI：
• 作为产物：
  描述：

  5-氟尿嘧啶核苷 在 吡啶 、 对甲苯磺酸 作用下， 以 丙酮 为溶剂， 反应 5.0h， 生成 5-fluoro-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)uridine
  参考文献：
  名称：

  Synthesis and structure–activity relationship of uracil nucleotide derivatives towards the identification of human P2Y 6 receptor antagonists

  摘要：

  P2Y(6) receptor (P2Y(6)-R) is involved in various physiological and pathophysiological events. With a view to set rules for the design of UDP-based reversible P2Y(6)-R antagonists as potential drugs, we established structure-activity relationship of UDP analogues, bearing modifications at the uracil ring, ribose moiety, and the phosphate chain. For instance, C5-phenyl- or 3-NMe-uridine-5'-alpha,beta-methylene-diphosphonate, 16 and 23, or lack of 2'-OH, in 12-15, resulted in loss of both agonist and antagonist activity toward hP2Y(6)-R. However, uridylyl phosphosulfate, 19, selectively inhibited hP2Y(6)-R (IC50 112 mu M) versus P2Y(2)/(4)-Rs. In summary, we have established a comprehensive SAR for hP2Y(6)-R ligands towards the development of hP2Y(6)-R antagonists. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.004

文献信息

• Introduction of an alkyl group into the sugar portion of uracilnucleosides by the use of Gilman reagents.
  作者：Hiroyuki HAYAKAWA、Hiroshi ASHIZAWA、Hiromichi TANAKA、Tadashi MIYASAKA

  DOI：10.1248/cpb.38.355

  日期：——

  Substitution of a p-toluenesulfonyloxy group in the sugar portion of uracilnucleosides by an alkyl group was investigated by using Gilman reagents (R2CuLi). In the cases of 5'-O-tosyl derivatives of 2', 3'-O-isopropylideneuridine, moderate vields of 5'-alkylated products were obtained. In contrast to this, the reactions of the corresponding 2'-deoxyuridine derivatives gave higher yields of products. A similar substitution reaction at the 3'-position of 2'-deoxyuridine derivatives was also examined.

  用Gilman试剂（R2CuLi）研究了尿嘧啶核苷糖部分的p-甲苯磺酰氧基被烷基取代的反应。对于2',3'-O-异亚丙基尿苷的5'-O-甲苯磺酸衍生物，得到了中等收率的5'-烷基化产物。与此相反，相应的2'-脱氧尿苷衍生物的反应则得到了更高收率的产物。还考察了在2'-脱氧尿苷衍生物的3'位进行类似取代反应的情况。
• Process for the preparation of a deoxyuridine derivative
  申请人：Pro.Bio.Sint SRL

  公开号：US20020128467A1

  公开（公告）日：2002-09-12

  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 -fluor o uridine thus obtained, is described.

  描述了一种制备5'-去氧-5-氟尿苷的方法，包括将2'，3'-O-异丙基-5-氟尿苷转化为相应的5'-O-磺酰衍生物，随后与碱性或碱土金属碘化物发生反应，然后水解异丙基亚甲基基团，还包括还原所得的5'-去氧-5'-碘-5-氟尿苷。
• Synthesis and in vivo antitumor activity of potential 5-fluorouracil prodrugs
  作者：A. Rosowsky、S. H. Kim、D. Trites、M. Wick

  DOI：10.1021/jm00351a006

  日期：1982.9
• Porphyrinyl-nucleosides containing fluorinated nucleobases
  作者：Leszek Czuchajowski、Anna Palka、Matthew Morra、Vinay Wandrekar

  DOI：10.1016/s0040-4039(00)73921-9

  日期：1993.1

  Porphyrins were synthesized in which a meso-p-phenylene-0- bridge joins the porphine core with 6-C of 5-fluorouridine (protected), 5-CF3-thymidine or 2-N-trifluoroacetamidato-6-0-pentafluorophenyl-2'-deoxyguanosine.
• 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.