dimethyl 4-amino-4-deoxy-10-carboxy-8,10-dideazapteroate | 88392-93-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: dimethyl 4-amino-4-deoxy-10-carboxy-8,10-dideazapteroate
• 英文别名: 4-amino-4-deoxy-10-carbomethoxy-8,10-dideazapteroate
• CAS: 88392-93-2
• 化学式: C₁₉H₁₉N₅O₄
• 分子量: 381.391
• InChiKey: ZXMDGQJYXJHYIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.48
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  dimethyl 4-amino-4-deoxy-10-carboxy-8,10-dideazapteroate 在 氰化钠 、 三乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 diethyl (2S)-2-[[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]amino]pentanedioate
  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 、 2,4-diamino-6-(bromomethyl)pyrido<3,2-d>pyrimidine 在 potassium hydride 作用下， 生成 dimethyl 4-amino-4-deoxy-10-carboxy-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

• Synthesis and antifolate properties of 5,10-methylenetetrahydro-8,10-dideazaminopterin
  作者：J. I. DeGraw、W. T. Colwell、R. L. Kisliuk、Y. Gaumont、F. M. Sirotnak

  DOI：10.1021/jm00159a039

  日期：1986.9

  The synthesis of the 5,10-methylene analogue of 5,6,7,8-tetrahydro-8,10-dideazaminopterin, a potential dual inhibitor of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzymes, is described. The dimethyl ester of 10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid was converted to the tetrahydro derivative by hydrogenation. Thermally induced cyclization of the 10-carbomethoxy and the 5-NH groups afforded the 5,10-carbonyl analogue. Reduction of the lactam with borane readily yielded the key 5,10-methylene-4-amino-4-deoxy-8,10-dideazatetrahydropteroic acid methyl ester. Saponification of the benzoate ester and coupling with L-glutamate concluded the synthesis. The title compound was a modest inhibitor of growth in folate-dependent bacteria. Streptococcus faecium and Lactobacillus casei, but inhibition of DHFR or TS derived from L. casei was poor. The compound was also a weak inhibitor of DHFR derived from L1210 murine leukemia and was a weak inhibitor of L1210 growth in culture.