N4-butyryl-4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one | 55726-29-9

• 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: N4-butyryl-4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• 英文别名: N-butyrylaracytidine；1-β-D-arabinofuranosyl-4-butyrylamino-1H-pyrimidin-2-one；N⁴-Butyryl-1-β-D-arabinofuranosylcytosin；N4-butyryl-1-beta-D-arabinofuranosylcytosine；N-[1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]butanamide
• CAS: 55726-29-9
• 化学式: C₁₃H₁₉N₃O₆
• 分子量: 313.31
• InChiKey: AVLGHOYUNPEBMO-KPQFEUGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Acetoneoxime butyrate 、 N4-butyryl-4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one 以 四氢呋喃 为溶剂， 反应 6.0h， 以84%的产率得到N,5'-O-dibutyrylaracytidine
  参考文献：
  名称：

  Enzymatic acylation and alkoxycarbonylation of α-, xylo-, anhydro-, and arabino-nucleosides.

  摘要：

  5'-O-acyl and 5'-O-alkoxycarbonyl derivatives of alpha-, anhydro-, xylo - and arabinonucleosides could be obtained through a lipase-mediated reaction with SP 435 lipase (from Candida antartica) by using acetoxyime butyrate or butyric anhydride, together with benzyloxycarbonyl-O-acetoxime as acylating agents Alkoxycarbonylation gave poorer yields than acylation and other lipases tested gave non-selective reaction or not reaction at all.

  DOI：

  10.1016/s0040-4020(01)80204-0
• 作为产物：
  描述：

  butyric O-ethyl-carbonic anhydride 、 阿糖胞苷 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以1.2 g的产率得到N4-butyryl-4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
  参考文献：
  名称：

  In-vitro transdermal penetration of cytarabine and its N4-alkylamide derivatives

  摘要：

  Objectives The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties.Methods The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n-octanol-water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity.Key findings The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (J(ss)) of 89.0 nmol/cm(2) per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm(2) per h).Conclusions The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine.

  DOI：

  10.1211/jpp.62.06.0012

文献信息

• N.sup.4 -acylarabinonucleosides
  申请人：Asahi Kasei Kogyo Kabushiki Kaisha

  公开号：US03991045A1

  公开（公告）日：1976-11-09

  An N.sup.4 -acyl-1-.beta.-D-arabinofuranosylcytosine having the following formula ##SPC1## Wherein R is an aliphatic acyl group having 3 to 35 carbon atoms. The compounds of this invention are useful as a cancer chemotherapeutic agent for controlling tumors, e.g., in mice, an insecticide, and a fungicidal surface active agent.

  具有以下公式的N.sup.4-酰基-1-.beta.-D-阿拉伯呋喃核苷酸：##SPC1##其中，R是具有3到35个碳原子的脂肪族酰基基团。本发明化合物可用作癌症化疗药物，用于控制肿瘤，例如在小鼠中，也可用作杀虫剂和杀真菌表面活性剂。
• ISIDA, TORAO;AKIYAMA, MINORU;OISI, DZYUNITI
  作者：ISIDA, TORAO、AKIYAMA, MINORU、OISI, DZYUNITI

  DOI：——

  日期：——
• Enzymatic acylation and alkoxycarbonylation of α-, xylo-, anhydro-, and arabino-nucleosides.
  作者：Francisco Morís、Gotor Vicente

  DOI：10.1016/s0040-4020(01)80204-0

  日期：1993.1

  5'-O-acyl and 5'-O-alkoxycarbonyl derivatives of alpha-, anhydro-, xylo - and arabinonucleosides could be obtained through a lipase-mediated reaction with SP 435 lipase (from Candida antartica) by using acetoxyime butyrate or butyric anhydride, together with benzyloxycarbonyl-O-acetoxime as acylating agents Alkoxycarbonylation gave poorer yields than acylation and other lipases tested gave non-selective reaction or not reaction at all.
• In-vitro transdermal penetration of cytarabine and its N4-alkylamide derivatives
  作者：Lesetja J. Legoabe、Jaco C. Breytenbach、David D. N'Da、J. Wilma Breytenbach

  DOI：10.1211/jpp.62.06.0012

  日期：2010.6

  Objectives The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties.Methods The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n-octanol-water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity.Key findings The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (J(ss)) of 89.0 nmol/cm(2) per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm(2) per h).Conclusions The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine.