9-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)nonanoic acid | 1477520-02-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 9-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)nonanoic acid
• 英文别名: 9-(2-Amino-4-oxo-3,7-dihydropyrrolo[2,3-d]pyrimidin-6-yl)nonanoic acid；9-(2-amino-4-oxo-3,7-dihydropyrrolo[2,3-d]pyrimidin-6-yl)nonanoic acid
• CAS: 1477520-02-7
• 化学式: C₁₅H₂₂N₄O₃
• 分子量: 306.365
• InChiKey: SQEUPDXSHKECRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)nonanoic acid 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (S)-2-(9-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]-pyrimidin-6-yl)nonanamido)pentanedioic acid
  参考文献：
  名称：

  Tumor-Targeting with Novel Non-Benzoyl 6-Substituted Straight Chain Pyrrolo[2,3-d]pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and Inhibition of de Novo Purine Nucleotide Biosynthesis

  摘要：

  A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d with varying chain lengths (n = 5-8) was designed and synthesized as part of our program to provide targeted antitumor agents with folate receptor (FR) cellular uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase) inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and reacted with diazomethane, followed by 48% HBr to generate the alpha-bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with 5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and subsequent coupling with diethyl L-glutamate and saponification afforded target compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FR alpha and -beta, associated with high affinity binding and inhibition of de novo purine nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR-expressing Chinese hamster cells and human KB tumor cells in culture. Our studies establish, for the first time, that a side chain benzoyl group is not essential for tumor-selective drug uptake by FR alpha.

  DOI：

  10.1021/jm401139z
• 作为产物：
  描述：

  癸二酸单甲酯 在 草酰氯 、 sodium hydroxide 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 75.67h， 生成 9-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)nonanoic acid
  参考文献：
  名称：

  Tumor-Targeting with Novel Non-Benzoyl 6-Substituted Straight Chain Pyrrolo[2,3-d]pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and Inhibition of de Novo Purine Nucleotide Biosynthesis

  摘要：

  A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d with varying chain lengths (n = 5-8) was designed and synthesized as part of our program to provide targeted antitumor agents with folate receptor (FR) cellular uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase) inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and reacted with diazomethane, followed by 48% HBr to generate the alpha-bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with 5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and subsequent coupling with diethyl L-glutamate and saponification afforded target compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FR alpha and -beta, associated with high affinity binding and inhibition of de novo purine nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR-expressing Chinese hamster cells and human KB tumor cells in culture. Our studies establish, for the first time, that a side chain benzoyl group is not essential for tumor-selective drug uptake by FR alpha.

  DOI：

  10.1021/jm401139z

文献信息

• Tumor-Targeting with Novel Non-Benzoyl 6-Substituted Straight Chain Pyrrolo[2,3-<i>d</i>]pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and Inhibition of de Novo Purine Nucleotide Biosynthesis
  作者：Yiqiang Wang、Christina Cherian、Steven Orr、Shermaine Mitchell-Ryan、Zhanjun Hou、Sudhir Raghavan、Larry H. Matherly、Aleem Gangjee

  DOI：10.1021/jm401139z

  日期：2013.11.14

  A new series of 6-substituted straight side chain pyrrolo[2,3-d]pyrimidines 3a-d with varying chain lengths (n = 5-8) was designed and synthesized as part of our program to provide targeted antitumor agents with folate receptor (FR) cellular uptake specificity and glycinamide ribonucleotide formyltransferase (GARFTase) inhibition. Carboxylic acids 4a-d were converted to the acid chlorides and reacted with diazomethane, followed by 48% HBr to generate the alpha-bromomethylketones 5a-d. Condensation of 2,4-diamino-6-hydroxypyrimidine 6 with 5a-d afforded the 6-substituted pyrrolo[2,3-d]pyrimidines 7a-d. Hydrolysis and subsequent coupling with diethyl L-glutamate and saponification afforded target compounds 3a-d. Compounds 3b-d showed selective cellular uptake via FR alpha and -beta, associated with high affinity binding and inhibition of de novo purine nucleotide biosynthesis via GARFTase, resulting in potent inhibition against FR-expressing Chinese hamster cells and human KB tumor cells in culture. Our studies establish, for the first time, that a side chain benzoyl group is not essential for tumor-selective drug uptake by FR alpha.