dibenzyl methotrexate | 60219-06-9

• 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: dibenzyl methotrexate
• CAS: 60219-06-9
• 化学式: C₃₄H₃₄N₈O₅
• 分子量: 634.695
• InChiKey: VQIPKIZPEATZLC-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  47.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  188.54
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为产物：
  描述：

  4-[N-(2,4-二氨基-6-蝶啶甲基)-N-甲氨基]苯甲酸半盐酸盐n水 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 生成 dibenzyl methotrexate
  参考文献：
  名称：

  Methotrexate analogs. 19. Enhancement of the antitumor effect of methotrexate and 3',5'-dichloromethotrexate by the use of lipid-soluble diesters

  摘要：

  Lipophilic methotrexate (MTX) and 3',5'-dichloromethotrexate (DCM) diesters were prepared by HCl-catalyzed esterification or by neutral esterification using cesium carbonate and an alkyl or aralkyl halide in Me2SO. The products were tested for in vivo antitumor activity against L1210 leukemia in mice to test whether all MTX and DCM diesters are therapeutically equivalent in this species. Contrary to what has been found with simple primary dialkyl esters, ortho-substituted dibenzyl esters of MTX produce longer survival on a q3dX3 schedule than does MTX itself and show a dose-sparing effect comparable to that of MTX at shorter treatment intervals. Thus, MTX bis(6-chloropiperonyl) ester at an MTX-equivalent dose of 5.5 mg/kg gave a +88% increase in median life span (ILS), whereas for MTX a +88% ILS required 30 mg/kg. When the MTX-equivalent dose of MTX bis(6-chloropiperonyl) ester was increased to 40 mg/kg, a +167% ILS was observed, as compared with a +100% ILS with 60 mg/kg of the parent drug. High activity (greater than 100% ILS) was likewise shown by the bis(2,5-dimethylbenzyl), bis(2,6-dichlorobenzyl), and di-3-picolyl esters of MTX and by the bis(1-methylbutyl) ester of DCM. The results of this study indicate that MTX and DCM esters are not therapeutically equivalent in mice, despite the high serum esterase activity in this species, and that an up to 10-fold reduction in total administered dose on the q3dX3 schedule is feasible by this approach.

  DOI：

  10.1021/jm00364a017

文献信息

• [EN] CROSSLINKED POLYMER NANOPARTICLES FOR TARGETED CELLULAR UPTAKE AND THERAPEUTICS, AND COMPOSITIONS AND METHODS THEREOF<br/>[FR] NANOPARTICULES POLYMÈRES RÉTICULÉES POUR ABSORPTION CELLULAIRE CIBLÉE ET AGENTS THÉRAPEUTIQUES, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：UNIV MASSACHUSETTS

  公开号：WO2018209006A1

  公开（公告）日：2018-11-15

  The invention provides novel compounds, pharmaceutical compositions and methods of preparation and therapeutic use thereof. The invention also provides novel gel compositions comprising hyaluronic acid (HA) polymers that are crosslinked with appropriate reversible crosslinkers and encapsulation of therapeutics or other payloads in such gel composition and nanoparticles thereof. The invention also relates to targeted delivery of such gel compositions and nanoparticles to specific cell types in a controllable delivery and release. The invention additionally relates to methods of therapeutic use of such gel compositions and nanoparticles in treatment of various diseases and conditions. The invention further relates to methods of preparation of the gel compositions and nanoparticles disclosed herein.

  本发明提供了新型化合物、制药组合物及其制备方法和治疗用途。本发明还提供了包含适当可逆交联剂交联的透明质酸（HA）聚合物的新型凝胶组合物，以及在这种凝胶组合物和纳米颗粒中封装治疗药物或其他有效载荷的方法。本发明还涉及将这种凝胶组合物和纳米颗粒定向递送到特定细胞类型的可控递送和释放。本发明还涉及使用这种凝胶组合物和纳米颗粒治疗各种疾病和病况的治疗方法。本发明还涉及所述凝胶组合物和纳米颗粒的制备方法。