卡培他滨中间体1 | 162204-19-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 中文名称: 卡培他滨中间体1
• 英文名称: (2R,3R,4R,5R)-2-(4-((Butoxycarbonyl)amino)-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyltetrahydrofuran-3,4-diyl diacetate
• 英文别名: [(2R,3R,4R,5R)-4-acetyloxy-5-[4-(butoxycarbonylamino)-5-fluoro-2-oxopyrimidin-1-yl]-2-methyloxolan-3-yl] acetate
• CAS: 162204-19-5
• 化学式: C₁₈H₂₄FN₃O₈
• 分子量: 429.402
• InChiKey: PKXRGASHOJQDLD-APGPQJPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  卡培他滨中间体1 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 5'-deoxy-5-fluoro-N⁴-(butoxycarbonyl)cytidine
  参考文献：
  名称：

  The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine

  摘要：

  To identify an orally available fluoropyrimidine having efficacy and safety profiles greatly improved over those of parenteral 5-fluorouracil (5-FU: 1), we designed a 5-FU prodrug that would pass intact through the intestinal mucisa and be sequentially converted to 5-FU by enzymes that are highly expressed in the human liver and then in tumors. Among various N-4-substituted 5'-deoxy-5-fluorocytidine derivatives, a series of N-4-alkoxycarbonyl derivatives were hydrolyzed to 5'-deoxy-5-fluoro-cytidine (5'-DFCR: 8) specifically by carboxylesterase, which exists preferentially in the liver in humans and monkeys. Particularly, derivatives having an N-4-alkoxylcarbonyl moiety with a C4-C6 alkyl chain were the most susceptible to the human carboxylesterase. Those were then converted to 5'-deoxy-5-fluorouridine (5'-DFUR: 4) by cytidine deaminase highly expressed in the liver and solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in turners. When administered orally to monkeys, a derivative having the N-4-alkoxylcarbonyl moiety with a C5 alkyl chain (capecitabine: 6) The highest AUC and Cmax for plasma 5'-DFUR. In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00087-0
• 作为产物：
  描述：

  1,2,3-三乙酰氧基-5-脱氧-D-核糖 在 吡啶 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 5.0h， 生成 卡培他滨中间体1
  参考文献：
  名称：

  The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine

  摘要：

  To identify an orally available fluoropyrimidine having efficacy and safety profiles greatly improved over those of parenteral 5-fluorouracil (5-FU: 1), we designed a 5-FU prodrug that would pass intact through the intestinal mucisa and be sequentially converted to 5-FU by enzymes that are highly expressed in the human liver and then in tumors. Among various N-4-substituted 5'-deoxy-5-fluorocytidine derivatives, a series of N-4-alkoxycarbonyl derivatives were hydrolyzed to 5'-deoxy-5-fluoro-cytidine (5'-DFCR: 8) specifically by carboxylesterase, which exists preferentially in the liver in humans and monkeys. Particularly, derivatives having an N-4-alkoxylcarbonyl moiety with a C4-C6 alkyl chain were the most susceptible to the human carboxylesterase. Those were then converted to 5'-deoxy-5-fluorouridine (5'-DFUR: 4) by cytidine deaminase highly expressed in the liver and solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in turners. When administered orally to monkeys, a derivative having the N-4-alkoxylcarbonyl moiety with a C5 alkyl chain (capecitabine: 6) The highest AUC and Cmax for plasma 5'-DFUR. In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00087-0

文献信息

• N-Oxycarbonyl substituted 5'-deoxy-5-fluorocytidines
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0602454B1

  公开（公告）日：1996-04-24