Nα-<4-(methylamino)benzoyl>-Nδ-<2-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl ester | 140914-27-8

• 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: Nα-<4-(methylamino)benzoyl>-Nδ-<2-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl ester
• 英文别名: N^α-<4-(methylamino)benzoyl>-N^δ-<2-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl ester；N^α-[4-(methylamino)benzoyl]-N^δ-(2-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl)glutamine benzyl ester
• CAS: 140914-27-8
• 化学式: C₃₄H₅₁N₃O₁₂P₂
• 分子量: 755.739
• InChiKey: YVGUAJSQFAOJBF-XLTVJXRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  51.0
• 可旋转键数：
  24.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  193.89
• 氢给体数：
  3.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  Nα-<4-(methylamino)benzoyl>-Nδ-<2-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl ester 在 甲醇 、 三甲基溴硅烷 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 52.5h， 生成
  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：

  1-benzyl L-glutamate 在 sodium hydroxide 、 potassium dihydrogenphosphate 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 28.83h， 生成 Nα-<4-(methylamino)benzoyl>-Nδ-<2-ethoxycarbonyl-3,3-bis(diethylphosphono)propyl>glutamine benzyl 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