4-{[8-carbamoyl-7-(3,5-dimethoxyphenylamino)imidazo[1,2-c]pyrimidin-5-ylamino]methyl}benzoic acid | 725235-16-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-{[8-carbamoyl-7-(3,5-dimethoxyphenylamino)imidazo[1,2-c]pyrimidin-5-ylamino]methyl}benzoic acid
• 英文别名: Imidazo[1,2-c]pyrimidine-8-carboxamide, 11；4-[[[8-carbamoyl-7-(3,5-dimethoxyanilino)imidazo[1,2-c]pyrimidin-5-yl]amino]methyl]benzoic acid
• CAS: 725235-16-5
• 化学式: C₂₃H₂₂N₆O₅
• 分子量: 462.465
• InChiKey: XLQAOMGZOHXTTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-{[8-carbamoyl-7-(3,5-dimethoxyphenylamino)imidazo[1,2-c]pyrimidin-5-ylamino]methyl}benzoic acid 在 N,N'-羰基二咪唑 、 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以57%的产率得到5-(4-carbamoylbenzylamino)-7-(3,5-dimethoxyphenylamino)imidazo[1,2-c]pyrimidine-8-carboxamide
  参考文献：
  名称：

  Structure–activity relationship studies of 5-benzylaminoimidazo[1,2-c]pyrimidine-8-carboxamide derivatives as potent, highly selective ZAP-70 kinase inhibitors

  摘要：

  Zeta-associated protein, 70 kDa (ZAP-70), a spleen tyrosine kinase (Syk) family kinase, is normally expressed on T cells and natural killer cells and plays a crucial role in activation of the T cell immunoresponse. Thus, selective ZAP-70 inhibitors might be useful not only for treating autoimmune diseases, but also for suppressing organ transplant rejection. In our recent study on the synthesis of Syk family kinase inhibitors, we discovered that novelimidazo[1,2-c]pyrimidine-8-carboxamide derivatives possessed potent ZAP-70 inhibitory activity with good selectivity for ZAP-70 over other kinases. In particular, compound 26 showed excellent ZAP-70 kinase inhibition and high selectivity for ZAP-70 over structurally related Syk. The discovery of a potent, highly selective ZAP-70 inhibitor would contribute a new therapeutic tool for autoimmune diseases and organ transplant medication. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.070
• 作为产物：
  描述：

  methyl 4-{[8-carbamoyl-7-(3,5-dimethoxyphenylamino)imidazo[1,2-c]pyrimidin-5-ylamino]methyl}benzoate 在 甲醇 、 sodium hydroxide 、 盐酸 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以66%的产率得到4-{[8-carbamoyl-7-(3,5-dimethoxyphenylamino)imidazo[1,2-c]pyrimidin-5-ylamino]methyl}benzoic acid
  参考文献：
  名称：

  Structure–activity relationship studies of 5-benzylaminoimidazo[1,2-c]pyrimidine-8-carboxamide derivatives as potent, highly selective ZAP-70 kinase inhibitors

  摘要：

  Zeta-associated protein, 70 kDa (ZAP-70), a spleen tyrosine kinase (Syk) family kinase, is normally expressed on T cells and natural killer cells and plays a crucial role in activation of the T cell immunoresponse. Thus, selective ZAP-70 inhibitors might be useful not only for treating autoimmune diseases, but also for suppressing organ transplant rejection. In our recent study on the synthesis of Syk family kinase inhibitors, we discovered that novelimidazo[1,2-c]pyrimidine-8-carboxamide derivatives possessed potent ZAP-70 inhibitory activity with good selectivity for ZAP-70 over other kinases. In particular, compound 26 showed excellent ZAP-70 kinase inhibition and high selectivity for ZAP-70 over structurally related Syk. The discovery of a potent, highly selective ZAP-70 inhibitor would contribute a new therapeutic tool for autoimmune diseases and organ transplant medication. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.070