2-pivaloylamino-4-oxo-6-benzylpyrrolo[2,3-d]pyrimidine | 1240384-09-1

• 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: 2-pivaloylamino-4-oxo-6-benzylpyrrolo[2,3-d]pyrimidine
• CAS: 1240384-09-1
• 化学式: C₁₈H₂₀N₄O₂
• 分子量: 324.382
• InChiKey: PJBLQCPDSWXSFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  90.64
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-pivaloylamino-4-oxo-6-benzylpyrrolo[2,3-d]pyrimidine 在 三氯氧磷 作用下， 以31%的产率得到2-pivaloylamino-4-chloro-6-benzylpyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Design, synthesis and evaluation of 2-amino-4-m-bromoanilino-6-arylmethyl-7H-pyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors and antiangiogenic agents1

  摘要：

  A series of 2-amino-4-m-bromoanilino-6-benzyl pyrrolo[ 2,3-d] pyrimidines analogues 4-12 were synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). These analogues were synthesized from the appropriate alpha-bromomethylbenzylketones via cyclocondensation with 2,6-diamino-4-pyrimidone to afford the 2-amino-4-oxo-6-substituted benzyl pyrrolo[ 2,3-d] pyrimidines. Chlorination at the 4-position followed by displacement with 3-bromoaniline or 3-bromo-N-methylaniline and methylation of the 7-NH afforded the target compounds. Remarkably, dimethylation of both the 4-N and N7 afford whole cell EGFR inhibitors that are more cytotoxic than clinically used erlotinib and mono-methylation at the 4-N or N7 affords more cytotoxic whole cell PDGFR-b inhibitors than clinically used sunitinib. Methylation at either the 4-N or N7 position was detrimental to whole cell VEGFR-2 inhibition. The inhibitory data against the RTKs in this study demonstrates that methylation of the 4-NH and/or the 7-NH influences both the specificity and potency of RTK inhibition. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.049
• 作为产物：
  描述：

  三甲基乙酸酐 、 2-amino-4-oxo-6-benzyl-3,7-dihydropyrrolo[2,3-d]pyrimidine 反应 3.0h， 以71%的产率得到2-pivaloylamino-4-oxo-6-benzylpyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Design, synthesis and evaluation of 2-amino-4-m-bromoanilino-6-arylmethyl-7H-pyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors and antiangiogenic agents1

  摘要：

  A series of 2-amino-4-m-bromoanilino-6-benzyl pyrrolo[ 2,3-d] pyrimidines analogues 4-12 were synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). These analogues were synthesized from the appropriate alpha-bromomethylbenzylketones via cyclocondensation with 2,6-diamino-4-pyrimidone to afford the 2-amino-4-oxo-6-substituted benzyl pyrrolo[ 2,3-d] pyrimidines. Chlorination at the 4-position followed by displacement with 3-bromoaniline or 3-bromo-N-methylaniline and methylation of the 7-NH afforded the target compounds. Remarkably, dimethylation of both the 4-N and N7 afford whole cell EGFR inhibitors that are more cytotoxic than clinically used erlotinib and mono-methylation at the 4-N or N7 affords more cytotoxic whole cell PDGFR-b inhibitors than clinically used sunitinib. Methylation at either the 4-N or N7 position was detrimental to whole cell VEGFR-2 inhibition. The inhibitory data against the RTKs in this study demonstrates that methylation of the 4-NH and/or the 7-NH influences both the specificity and potency of RTK inhibition. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.049