5-fluoro-O^3'_,O5'-dipropionyl-2'-deoxy-uridine | 4564-21-0

• 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-fluoro-O^3'_,O5'-dipropionyl-2'-deoxy-uridine
• 英文别名: 2'-Deoxy-3',5'-di-O-n-propionyl-5-fluorouridine；2'-deoxy-3',5'-di-O-propionyl-5-fluorouridine；[(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-propanoyloxyoxolan-2-yl]methyl propanoate
• CAS: 4564-21-0
• 化学式: C₁₅H₁₉FN₂O₇
• 分子量: 358.323
• InChiKey: AFHGVBAFDUCQAI-HBNTYKKESA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  邻甲基苯甲酰氯 、 5-fluoro-O^3'_,O5'-dipropionyl-2'-deoxy-uridine 在 三乙胺 作用下， 以 1,4-二氧六环 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 二甲基亚砜 为溶剂， 以56.4%的产率得到3-(2-methylbenzoyl)-2'-deoxy-3',5'-di-O-propionyl-5-fluorouridine
  参考文献：
  名称：

  2'-Deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine derivatives, a process

  摘要：

  2'-脱氧-3',5'-双-O-烷基羰基-5-氟尿苷衍生物具有强烈的抗肿瘤活性，毒性较弱，通式如下：其中R代表一个烷基团、一个烷氧基团或一个卤原子，m为零或1-3的整数，n为1-14的整数，条件是当m为2或3时，R可能相同也可能不同，当m为2且相邻的两个R为烷氧基团时，这两个烷氧基团的两个烷基部分可以结合形成与两个相邻的氧桥连接成员一起形成一个烷二氧基基团。这些衍生物通过用相应的苯甲酰卤酸酐对2'-脱氧-3',5'-双-O-烷基羰基-5-氟尿苷进行酰化制备，可作为抗肿瘤药物的活性成分，特别适用于口服给药。

  公开号：

  US04503045A1

文献信息

• Activity of esterase in the hydrolysis of 3',5'-diesters of 5-fluoro-2'-deoxyuridine in relation to the structure of the diester prodrugs.
  作者：TAKEO KAWAGUCHI、YOSHIKI SUZUKI、YOKO NAKAHARA、NAOKI NAMBU、TSUNEJI NAGAI

  DOI：10.1248/cpb.33.301

  日期：——

  The activity of porcine liver esterase towards diesters of 5-fluoro-2'-deoxyuridine with saturated aliphatic acids including acetic, propionic, butyric, hexanoic, octanoic, decanoic and dodecanoic acids was investigated. The susceptibility of the 3', 5'-diesters increased as the acyl chain was lengthened up to octanoyl, but further increase in the acyl chain length resulted in a sharp decrease in the susceptibility. The susceptibility of 3'-and 5'-monoesters increased as the chain was lengthened to decanoyl and slightly decreased on going to dodecanoyl. These results suggest that the higher antitumor activity of longer alkyl chain diesters of 5-fluoro-2'-deoxyuridine is partly due to their slow rates of hydrolysis by non-specific esterase.

  研究了猪肝脏酯酶对 5-氟-2'-脱氧尿苷与饱和脂肪族酸（包括乙酸、丙酸、丁酸、己酸、辛酸、癸酸和十二酸）的二酯的活性。随着酰基链延长至辛酰，3', 5'-二酯的易感性增加，但酰基链长度的进一步增加导致易感性急剧下降。3'-和 5'-单酯的敏感性随着酰基链延长到癸酰基而增加，当延长到十二酰基时则略有下降。这些结果表明，5-氟-2'-脱氧尿苷的长烷基链二酯具有较高的抗肿瘤活性，部分原因是它们被非特异性酯酶水解的速度较慢。
• FUDZII, NORIO;YASUI, BOMPEHJ;MIYAMOTO, TOMOXISA;SIGA, MASATOSI;ANDO, KADZ+
  作者：FUDZII, NORIO、YASUI, BOMPEHJ、MIYAMOTO, TOMOXISA、SIGA, MASATOSI、ANDO, KADZ+

  DOI：——

  日期：——
• FUJII, SETSURO;YASUI, BOMPEI;MIYAMOTO, TOMOHISA;SHIGA, MASATOSHI;ANDO, KA+
  作者：FUJII, SETSURO、YASUI, BOMPEI、MIYAMOTO, TOMOHISA、SHIGA, MASATOSHI、ANDO, KA+

  DOI：——

  日期：——
• US4503045A
  申请人：——

  公开号：US4503045A

  公开（公告）日：1985-03-05
• 2'-Deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine derivatives, a process
  申请人：Funai Yakuhin Kogyo Kabushiki Kaisha

  公开号：US04503045A1

  公开（公告）日：1985-03-05

  2'-Deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine derivatives possessing strong anti-tumor activity with weak toxicity and represented by the general formula: ##STR1## wherein R stands for an alkyl group, an alkoxy group or a halogen atom, m for zero or an integer of 1-3, and n for an integer of 1-14, with the proviso that when m is 2 or 3, R's may be the same or different and that when m is 2 and the adjacent two R's are alkoxy groups, the two alkyl moieties of the alkoxy groups may be combined to form together with the two adjacent oxa bridging members an alkylenedioxy group as a whole. These derivatives are prepared by acylating a 2'-deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine with corresponding benzoyl halides and are useful as active ingredients for anti-tumor agents, especially for oral administration.

  2'-脱氧-3',5'-双-O-烷基羰基-5-氟尿苷衍生物具有强烈的抗肿瘤活性，毒性较弱，通式如下：其中R代表一个烷基团、一个烷氧基团或一个卤原子，m为零或1-3的整数，n为1-14的整数，条件是当m为2或3时，R可能相同也可能不同，当m为2且相邻的两个R为烷氧基团时，这两个烷氧基团的两个烷基部分可以结合形成与两个相邻的氧桥连接成员一起形成一个烷二氧基基团。这些衍生物通过用相应的苯甲酰卤酸酐对2'-脱氧-3',5'-双-O-烷基羰基-5-氟尿苷进行酰化制备，可作为抗肿瘤药物的活性成分，特别适用于口服给药。