N^α--N^δ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester | 147938-28-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N^α--N^δ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester
• 英文别名: N^α-(t-butyloxycarbonyl)-N^δ-(2,2-bis(diethylphosphono)ethyl)glutamine ethyl ester
• CAS: 147938-28-1
• 化学式: C₂₂H₄₄N₂O₁₁P₂
• 分子量: 574.546
• InChiKey: MZYZDSQEGXBHAN-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  37.0
• 可旋转键数：
  18.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  164.79
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N^α--N^δ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以70%的产率得到N^δ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester
  参考文献：
  名称：

  A study of the delivery-targeting concept applied to antineoplasic drugs active on human osteosarcoma. I. Synthesis and biological activity in nude mice carrying human osteosarcoma xenografts of gem-bisphosphonic methotrexate analogues

  摘要：

  With the aim of verifying the concept of osteotic vectorisation, synthesis of three methotrexate (MTX) gem-diphosphonic analogues (compounds A, B and C) was performed. These molecules were tested on BALB/c and NIH III mice previously grafted with subcutaneous implants of OHS, TTX p7 and/or TTX p11 human osteosarcoma cell lines. Antineoplasic activity of compound B and C (active compounds) was compared to the activity for MTX alone and to activity of compound A (inactive compound). Compounds B and C exhibited an increased antineoplasic activity compared to MTX alone and to compound A. At equimolar doses, compound B was found to be 5-6-fold more active than MTX given alone. We have discussed the concept of osteotic vectorisation of compound B, which could be regarded as a prodrug.

  DOI：

  10.1016/0223-5234(92)90117-j
• 作为产物：
  描述：

  L-谷氨酰胺 在 sodium hydroxide 、 potassium tert-butylate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 叔丁醇 为溶剂， 反应 98.0h， 生成 N^α--N^δ-<2,2-bis(diethylphosphono)ethyl>glutamine ethyl ester
  参考文献：
  名称：

  A study of the delivery-targeting concept applied to antineoplasic drugs active on human osteosarcoma. I. Synthesis and biological activity in nude mice carrying human osteosarcoma xenografts of gem-bisphosphonic methotrexate analogues

  摘要：

  With the aim of verifying the concept of osteotic vectorisation, synthesis of three methotrexate (MTX) gem-diphosphonic analogues (compounds A, B and C) was performed. These molecules were tested on BALB/c and NIH III mice previously grafted with subcutaneous implants of OHS, TTX p7 and/or TTX p11 human osteosarcoma cell lines. Antineoplasic activity of compound B and C (active compounds) was compared to the activity for MTX alone and to activity of compound A (inactive compound). Compounds B and C exhibited an increased antineoplasic activity compared to MTX alone and to compound A. At equimolar doses, compound B was found to be 5-6-fold more active than MTX given alone. We have discussed the concept of osteotic vectorisation of compound B, which could be regarded as a prodrug.

  DOI：

  10.1016/0223-5234(92)90117-j