4-amino-4-deoxy-10-methyl-10-carbomethoxy-8,10-dideazapteroate | 88392-94-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-amino-4-deoxy-10-methyl-10-carbomethoxy-8,10-dideazapteroate
• 英文别名: methyl 4-[3-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)-1-methoxy-2-methyl-1-oxopropan-2-yl]benzoate
• CAS: 88392-94-3
• 化学式: C₂₀H₂₁N₅O₄
• 分子量: 395.418
• InChiKey: YOCXGPHGXKBLIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.65
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  143.31
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4-amino-4-deoxy-10-methyl-10-carbomethoxy-8,10-dideazapteroate 在 氰化钠 作用下， 以 二甲基亚砜 为溶剂， 反应 2.5h， 以96%的产率得到4-amino-4-deoxy-10-methyl-8,10-dideazapteroic acid
  参考文献：
  名称：

  Synthesis and antifolate properties of 10-alkyl-8,10-dideazaminopterins

  摘要：

  The synthesis of 10-alkyl analogues of the potent antitumor agent 8,10-dideazaminopterin is described. Alkylation of appropriate alpha-alkyl homoterephthalate esters with 2,4-diamino-6-(bromomethyl)-8-deazapteridine afforded 10-alkyl-10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid diesters. Ester cleavage and decarboxylation at C-10 were accomplished by heating with sodium cyanide in Me2SO at 170-180 degrees C to afford the 2,4-diamino-10-alkyl-8,10-dideazapteroic acids. The acids were coupled with diethyl glutamate, followed by saponification, to give the 10-alkyl-8,10-dideazaminopterins. The compounds were potent inhibitors of growth in folate-dependent bacteria, Streptococcus faecium and Lactobacillus casei. The 10-methyl and 10-ethyl analogues gave the highest percent increases in life span for mice infected with L1210 leukemia with ILS values of +203 and +235%, respectively.

  DOI：

  10.1021/jm00369a024
• 作为产物：
  描述：

  4-甲酸甲酯苯乙酸甲酯 在 potassium hydride 作用下， 反应 3.5h， 生成 4-amino-4-deoxy-10-methyl-10-carbomethoxy-8,10-dideazapteroate
  参考文献：
  名称：

  Synthesis and antifolate properties of 10-alkyl-8,10-dideazaminopterins

  摘要：

  The synthesis of 10-alkyl analogues of the potent antitumor agent 8,10-dideazaminopterin is described. Alkylation of appropriate alpha-alkyl homoterephthalate esters with 2,4-diamino-6-(bromomethyl)-8-deazapteridine afforded 10-alkyl-10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid diesters. Ester cleavage and decarboxylation at C-10 were accomplished by heating with sodium cyanide in Me2SO at 170-180 degrees C to afford the 2,4-diamino-10-alkyl-8,10-dideazapteroic acids. The acids were coupled with diethyl glutamate, followed by saponification, to give the 10-alkyl-8,10-dideazaminopterins. The compounds were potent inhibitors of growth in folate-dependent bacteria, Streptococcus faecium and Lactobacillus casei. The 10-methyl and 10-ethyl analogues gave the highest percent increases in life span for mice infected with L1210 leukemia with ILS values of +203 and +235%, respectively.

  DOI：

  10.1021/jm00369a024

文献信息

• DEGRAW, J. I.;KELLY, L. F.;SIROTNAK, F. M.
  作者：DEGRAW, J. I.、KELLY, L. F.、SIROTNAK, F. M.

  DOI：——

  日期：——