4,4-Bis-(diethoxy-phosphoryl)-2-{4-[methyl-(2,2,2-trichloro-ethoxycarbonyl)-amino]-benzoylamino}-butyric acid ethyl ester | 120355-33-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,4-Bis-(diethoxy-phosphoryl)-2-{4-[methyl-(2,2,2-trichloro-ethoxycarbonyl)-amino]-benzoylamino}-butyric acid ethyl ester
• 英文别名: Ethyl 4,4-bis(diethoxyphosphoryl)-2-[[4-[methyl(2,2,2-trichloroethoxycarbonyl)amino]benzoyl]amino]butanoate
• CAS: 120355-33-1
• 化学式: C₂₅H₃₉Cl₃N₂O₁₁P₂
• 分子量: 711.898
• InChiKey: WBUIWFCVJSLVRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  43
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  156
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4,4-Bis-(diethoxy-phosphoryl)-2-{4-[methyl-(2,2,2-trichloro-ethoxycarbonyl)-amino]-benzoylamino}-butyric acid ethyl ester 在 potassium dihydrogenphosphate 、 锌 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 生成 tetraethyl 3-ethoxycarbonyl-N-<4-(methylamino)benzoyl>-3-aminopropylidene-1,1-bisphosphonate
  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：

  ethyl 2-amino-4,4-bis(diethoxyphosphoryl)butyrate 、 2,2,2-trichloroethyl N-(4-carbonochloridoylphenyl)-N-methylcarbamate 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以70%的产率得到4,4-Bis-(diethoxy-phosphoryl)-2-{4-[methyl-(2,2,2-trichloro-ethoxycarbonyl)-amino]-benzoylamino}-butyric acid 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

文献信息

• STURTZ, GEORGES LOUIS EDMOND;VOISIN, PATRICIA CECILE MARIE-LAURE
  作者：STURTZ, GEORGES LOUIS EDMOND、VOISIN, PATRICIA CECILE MARIE-LAURE

  DOI：——

  日期：——
• 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
  作者：G Sturtz、G Appéré、K Breistol、O Fodstad、G Schwartsmann、HR Hendriks

  DOI：10.1016/0223-5234(92)90117-j

  日期：1992.11

  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.