dicesium methotrexate | 86669-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: dicesium methotrexate
• 英文别名: di-cesium salt of methotrexate
• CAS: 86669-44-5
• 化学式: C₂₀H₂₀N₈O₅*2Cs
• 分子量: 718.24
• InChiKey: LMDMUGSSLRWSDP-ZOWNYOTGSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  34.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  216.2
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  3-氯甲基吡啶 、 dicesium methotrexate 以 二甲基亚砜 为溶剂， 反应 20.0h， 以31%的产率得到(S)-2-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-pentanedioic acid dipyridin-3-ylmethyl ester
  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
• 作为产物：
  描述：

  甲氨蝶呤 在 cesium bicarbonate 作用下， 以 水 为溶剂， 反应 4.0h， 生成 dicesium methotrexate
  参考文献：
  名称：

  Diagnostic or therapeutic somatostatin or bombesin analog conjugates and uses thereof

  摘要：

  披露了肽剂及其用途，它们是生物活性肽的类似物，例如生长抑素和蛙皮素。发明的化合物具有通式X-Y-Z-Q，其中X是细胞毒素、治疗剂、可检测的标签或螯合基团，Q是生物活性肽。在发明的肽剂中，Y是可选的水溶性聚合物或肽，Z是与Q的氨基端连接的连接肽，具有两个、三个、四个或五个氨基酸残基，选择将X连接到Q，同时保留Q的生物活性。还披露了使用这些肽剂在疾病的诊断和治疗中的方法。

  公开号：

  US20050070470A1