(2S)-2-[[4-[1-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)butan-2-yl]benzoyl]amino]pentanedioic acid | 88393-05-9

• 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: (2S)-2-[[4-[1-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)butan-2-yl]benzoyl]amino]pentanedioic acid
• CAS: 88393-05-9
• 化学式: C₂₃H₂₆N₆O₅
• 分子量: 466.497
• InChiKey: ODUVEXGYNIEOHD-TYJDENFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  194
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,4-diamino-6-(bromomethyl)pyrido<3,2-d>pyrimidine 在 sodium hydroxide 、 氰化钠 、 potassium hydride 、 三乙胺 作用下， 以 乙二醇甲醚 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 (2S)-2-[[4-[1-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)butan-2-yl]benzoyl]amino]pentanedioic 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

文献信息

• Synthesis and antifolate properties of 10-alkyl-8,10-dideazaminopterins
  作者：J. I. DeGraw、P. H. Christie、E. G. Brown、L. F. Kelly、R. L. Kisliuk、Y. Gaumont、F. M. Sirotnak

  DOI：10.1021/jm00369a024

  日期：1984.3

  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.