di-tert-butyl (S)-2-(4-(2-(3-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzamido)pentanedioate | 1050369-86-2

• 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: di-tert-butyl (S)-2-(4-(2-(3-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzamido)pentanedioate
• CAS: 1050369-86-2
• 化学式: C₃₁H₄₅N₅O₆S₂
• 分子量: 647.86
• InChiKey: DWQRZOQNASJNAH-QFIPXVFZSA-N

物化性质

• 熔点：
  120-124 °C
• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.54
• 重原子数：
  44.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  179.49
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  di-tert-butyl (S)-2-(4-(2-(3-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzamido)pentanedioate 在 三氟乙酸 作用下， 以 氯仿 为溶剂， 以91%的产率得到(S)-2-(4-(2-(3-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzamido)pentanedioic acid
  参考文献：
  名称：

  Asymmetric Synthesis of Inhibitors of Glycinamide Ribonucleotide Transformylase

  摘要：

  Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors and has emerged as a productive target for antineoplastic therapeutic intervention. The asymmetric synthesis and evaluation of the two diastereomers of 10-methylthio-DDACTHF (10R-3 and 10S-3) and related analogues as potential inhibitors of GAR Tfase are reported. This work, which defines the importance of the C10 stereochemistry for this class of inhibitors of GAR Tfase, revealed that both diastereomers are potent inhibitors of rhGAR Tfase (10R-3 K-i = 210 nM, 10S-3 K-i = 180 nM) that exhibit effective cell growth inhibition (CCRF-CEM IC50 80 and 50 nM, respectively), which is dependent on intracellular polyglutamation by folylpolyglutamate synthetase (FPGS) but not intracellular transport by the reduced folate carrier.

  DOI：

  10.1021/jm800555h
• 作为产物：
  描述：

  4-(2-(3-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzoic acid 、 L-谷氨酸二叔丁酯盐酸盐 在 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以75%的产率得到di-tert-butyl (S)-2-(4-(2-(3-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)propyl)-1,3-dithian-2-yl)benzamido)pentanedioate
  参考文献：
  名称：

  Asymmetric Synthesis of Inhibitors of Glycinamide Ribonucleotide Transformylase

  摘要：

  Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors and has emerged as a productive target for antineoplastic therapeutic intervention. The asymmetric synthesis and evaluation of the two diastereomers of 10-methylthio-DDACTHF (10R-3 and 10S-3) and related analogues as potential inhibitors of GAR Tfase are reported. This work, which defines the importance of the C10 stereochemistry for this class of inhibitors of GAR Tfase, revealed that both diastereomers are potent inhibitors of rhGAR Tfase (10R-3 K-i = 210 nM, 10S-3 K-i = 180 nM) that exhibit effective cell growth inhibition (CCRF-CEM IC50 80 and 50 nM, respectively), which is dependent on intracellular polyglutamation by folylpolyglutamate synthetase (FPGS) but not intracellular transport by the reduced folate carrier.

  DOI：

  10.1021/jm800555h