[[(2R,3R,4S,5R)-5-(4-氨基-2-氧代-嘧啶-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-羟基-磷酰]氧基-[(2R)-2,3-二十八碳酰氧基丙氧基]次磷酸 | 83214-11-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油磷脂
• 中文名称: [[(2R,3R,4S,5R)-5-(4-氨基-2-氧代-嘧啶-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-羟基-磷酰]氧基-[(2R)-2,3-二十八碳酰氧基丙氧基]次磷酸
• 中文别名: 1-氮杂螺[4.4]壬烷,6-(1-吡咯烷基)-,(5R,6R)-
• 英文名称: 1-β-D-arabinofuranosylcytosine 5'-diphosphate-L-1,2-distearin
• 英文别名: Ara-cdp-distearin；[(2R)-3-[[[(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-octadecanoyloxypropyl] octadecanoate
• CAS: 83214-11-3
• 化学式: C₄₈H₈₉N₃O₁₅P₂
• 分子量: 1010.19
• InChiKey: PDCWLWQTNQCGRI-LWVUIVPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.8
• 重原子数：
  68
• 可旋转键数：
  46
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  263
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  L-Alpha-二硬脂酰磷脂酰胆碱 在 吡啶 、 sodium acetate 、 sodium dodecyl-sulfate 、 溶剂黄146 、 calcium chloride 作用下， 以 乙醚 为溶剂， 反应 336.0h， 生成 [[(2R,3R,4S,5R)-5-(4-氨基-2-氧代-嘧啶-1-基)-3,4-二羟基-四氢呋喃-2-基]甲氧基-羟基-磷酰]氧基-[(2R)-2,3-二十八碳酰氧基丙氧基]次磷酸
  参考文献：
  名称：

  Phospholipid-nucleoside conjugates. 3. Syntheses and preliminary biological evaluation of 1-.beta.-D-arabinofuranosylcytosine 5'-monophosphate-L-1,2-dipalmitin and selected 1-.beta.-D-arabinofuranosylcytosine 5'-diphosphate-L-1,2-diacylglycerols

  摘要：

  Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable ara-CMP-L-dipalmitin-N-phosphoryldicyclohexylurea adduct was isolated as a crystalline solid (two diastereomers) in the reaction sequence to prepare ara-CMP-L-dipalmitin. The new prodrugs were solubilized by sonication methods and tested for their antiproliferative activity in vitro against mouse myeloma MPC-11 cells and against L1210 lymphoid leukemia. Such studies demonstrated that the antiproliferative activities of the prodrugs (as determined by ED50) were less that ara-C on a molar basis. In the mouse myeloma cell line some evidence was obtained that the antiproliferative activity was related to the chain length of the fatty acid side chains in the prodrugs. In in vivo studies against L1210 lymphoid leukemia in mice, the prodrugs were shown to be much more effective than ara-C, with the overall efficacy apparently being independent of the length of the fatty acid side chain. Some evidence was obtained in the vivo studies that the ara-CDP-L-dimyristin, which bears the shortest fatty acid side chain, was more toxic at the higher dosages than the longer chain length derivatives.

  DOI：

  10.1021/jm00353a010

文献信息

• Phospholipid-nucleoside conjugates. 3. Syntheses and preliminary biological evaluation of 1-.beta.-D-arabinofuranosylcytosine 5'-monophosphate-L-1,2-dipalmitin and selected 1-.beta.-D-arabinofuranosylcytosine 5'-diphosphate-L-1,2-diacylglycerols
  作者：Eung K. Ryu、Robert J. Ross、Tatsuo Matsushita、Malcolm MacCoss、Chung I. Hong、Charles R. West

  DOI：10.1021/jm00353a010

  日期：1982.11

  Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable ara-CMP-L-dipalmitin-N-phosphoryldicyclohexylurea adduct was isolated as a crystalline solid (two diastereomers) in the reaction sequence to prepare ara-CMP-L-dipalmitin. The new prodrugs were solubilized by sonication methods and tested for their antiproliferative activity in vitro against mouse myeloma MPC-11 cells and against L1210 lymphoid leukemia. Such studies demonstrated that the antiproliferative activities of the prodrugs (as determined by ED50) were less that ara-C on a molar basis. In the mouse myeloma cell line some evidence was obtained that the antiproliferative activity was related to the chain length of the fatty acid side chains in the prodrugs. In in vivo studies against L1210 lymphoid leukemia in mice, the prodrugs were shown to be much more effective than ara-C, with the overall efficacy apparently being independent of the length of the fatty acid side chain. Some evidence was obtained in the vivo studies that the ara-CDP-L-dimyristin, which bears the shortest fatty acid side chain, was more toxic at the higher dosages than the longer chain length derivatives.