(+)-1-(2-deoxy-2-fluoro-4-seleno-D-arabinofuranosyl)cytosine | 1187425-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (+)-1-(2-deoxy-2-fluoro-4-seleno-D-arabinofuranosyl)cytosine
• 英文别名: 2′ -F-4′ -Se-ara-C；2′ -F-4′ -seleno-ara-C；F–Se-Ara-C；4-amino-1-(3-fluoro-4-hydroxy-5-hydroxymethyl-tetrahydro-selenophen-2-yl)-1H-pyrimidin-2-one；2'-fluoro-4'-seleno-ara-C；4-amino-1-[(2R,3S,4S,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)selenolan-2-yl]pyrimidin-2-one
• CAS: 1187425-09-7
• 化学式: C₉H₁₂FN₃O₃Se
• 分子量: 308.171
• InChiKey: GLESYYOUKBSQNJ-PXBUCIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.48
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,3-O-异亚丙基-D-核糖酸 gamma-内酯 在 吡啶 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 selenium 、 sodium tetrahydroborate 、 二乙胺基三氟化硫 、 三氟甲磺酸三甲基硅酯 、 氨 、 水 、 4-甲基苯磺酸吡啶 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 丙酮 、 甲苯 、 乙腈 为溶剂， 反应 197.83h， 生成 (+)-1-(2-deoxy-2-fluoro-4-seleno-D-arabinofuranosyl)cytosine
  参考文献：
  名称：

  Structure–activity relationships of 2′-modified-4′-selenoarabinofuranosyl-pyrimidines as anticancer agents

  摘要：

  Based on the potent anticancer activity of the D-arabino-configured cytosine nucleoside ara-C, novel 2'-substituted-4'-selenoarabinofuranosyl pyrimidines 3a-3u, comprising azido, fluoro, and hydroxyl substituents at C-2' were designed, synthesized, and evaluated for anticancer activity. The 2'-azido group was stereoselectively introduced by the Mitsunobu reaction using diphenylphosphoryl azide (DPPA), and the 2'-fluoro group was stereoselectively introduced through the double inversions of stereochemistry via the episelenium intermediate, which was formed by the participation of the selenium atom. Among the compounds tested, the 2'-fluoro derivative 3t (X = NH2, Y = H, R = F) was found to be the most potent anticancer agent and showed more potent anticancer activity than the control, ara-C in all tested human cancer cell lines (HCT116, A549, SNU638, T47D, and PC-3) except the leukemia cell lines (K562). The anticancer activity of the 2'-substituted-4'-selenonucleosides is in the following order: 2'-F > 2'-OH > 2'-N3.

  DOI：

  10.1016/j.ejmech.2014.06.031

文献信息

• Discovery of a New Template for Anticancer Agents: 2′-deoxy-2′-fluoro-4′-selenoarabinofuranosyl-cytosine (2′-F-4′-Seleno-ara-C)
  作者：Lak Shin Jeong、Dilip K. Tosh、Won Jun Choi、Sang Kook Lee、You-Jin Kang、Sun Choi、Jin Hee Lee、Hankil Lee、Hyuk Woo Lee、Hea Ok Kim

  DOI：10.1021/jm900852b

  日期：2009.9.10

  The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).
• Structure–activity relationships of 2′-modified-4′-selenoarabinofuranosyl-pyrimidines as anticancer agents
  作者：Jin-Hee Kim、Jinha Yu、Varughese Alexander、Jung Hee Choi、Jayoung Song、Hyuk Woo Lee、Hea Ok Kim、Jungwon Choi、Sang Kook Lee、Lak Shin Jeong

  DOI：10.1016/j.ejmech.2014.06.031

  日期：2014.8

  Based on the potent anticancer activity of the D-arabino-configured cytosine nucleoside ara-C, novel 2'-substituted-4'-selenoarabinofuranosyl pyrimidines 3a-3u, comprising azido, fluoro, and hydroxyl substituents at C-2' were designed, synthesized, and evaluated for anticancer activity. The 2'-azido group was stereoselectively introduced by the Mitsunobu reaction using diphenylphosphoryl azide (DPPA), and the 2'-fluoro group was stereoselectively introduced through the double inversions of stereochemistry via the episelenium intermediate, which was formed by the participation of the selenium atom. Among the compounds tested, the 2'-fluoro derivative 3t (X = NH2, Y = H, R = F) was found to be the most potent anticancer agent and showed more potent anticancer activity than the control, ara-C in all tested human cancer cell lines (HCT116, A549, SNU638, T47D, and PC-3) except the leukemia cell lines (K562). The anticancer activity of the 2'-substituted-4'-selenonucleosides is in the following order: 2'-F > 2'-OH > 2'-N3.