5-(2-Amino-2-methylpropylamino)-7-(3,5-dimethoxyphenylamino)-1,2,4-triazolo[4,3-c]pyrimidine-8-carboxamide | 794462-22-9

• 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: 5-(2-Amino-2-methylpropylamino)-7-(3,5-dimethoxyphenylamino)-1,2,4-triazolo[4,3-c]pyrimidine-8-carboxamide
• 英文别名: 5-[(2-amino-2-methylpropyl)amino]-7-(3,5-dimethoxyanilino)-[1,2,4]triazolo[4,3-c]pyrimidine-8-carboxamide
• CAS: 794462-22-9
• 化学式: C₁₈H₂₄N₈O₃
• 分子量: 400.44
• InChiKey: ICLJPAGXKRSDCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  155
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl {2-[8-carbamoyl-7-(3,5-dimethoxyphenylamino)-1,2,4-triazolo[4,3-c]pyrimidin-5-ylamino]-1,1-dimethylethyl}carbamate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以21%的产率得到5-(2-Amino-2-methylpropylamino)-7-(3,5-dimethoxyphenylamino)-1,2,4-triazolo[4,3-c]pyrimidine-8-carboxamide
  参考文献：
  名称：

  A novel Syk family kinase inhibitor: Design, synthesis, and structure–activity relationship of 1,2,4-triazolo[4,3-c]pyrimidine and 1,2,4-triazolo[1,5-c]pyrimidine derivatives

  摘要：

  Splenic tyrosine kinase (Syk) family kinases, which are members of the protein tyrosine kinase family, play crucial roles in immune responses, with Syk participating in B-cell activation and the zeta-associated protein 70 kDa (ZAP-70) kinase being involved in T-cell activation. Therefore, Syk family kinase inhibitors are candidate therapeutic agents for the treatment of various allergic disorders and autoimmune diseases. We designed 1,2,4-triazolo[4,3-c] pyrimidine and 1,2,4-triazolo[1,5-c] pyrimidine derivatives as Syk family kinase inhibitors, based on literature reports and structure-based drug design. These derivatives showed significant Syk inhibitory activities, with ZAP-70 inhibition. Representative compounds 10d and 11 not only exhibited strong inhibition of both Syk and ZAP-70 kinase but also suppressed IL-2 production by peripheral blood mononuclear cells and whole blood. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.06.017

文献信息

• A novel Syk family kinase inhibitor: Design, synthesis, and structure–activity relationship of 1,2,4-triazolo[4,3-c]pyrimidine and 1,2,4-triazolo[1,5-c]pyrimidine derivatives
  作者：Akihito Hirabayashi、Harunobu Mukaiyama、Hiroaki Kobayashi、Hiroaki Shiohara、Satoko Nakayama、Motoyasu Ozawa、Keiji Miyazawa、Keiko Misawa、Hideki Ohnota、Masayuki Isaji

  DOI：10.1016/j.bmc.2008.06.017

  日期：2008.8

  Splenic tyrosine kinase (Syk) family kinases, which are members of the protein tyrosine kinase family, play crucial roles in immune responses, with Syk participating in B-cell activation and the zeta-associated protein 70 kDa (ZAP-70) kinase being involved in T-cell activation. Therefore, Syk family kinase inhibitors are candidate therapeutic agents for the treatment of various allergic disorders and autoimmune diseases. We designed 1,2,4-triazolo[4,3-c] pyrimidine and 1,2,4-triazolo[1,5-c] pyrimidine derivatives as Syk family kinase inhibitors, based on literature reports and structure-based drug design. These derivatives showed significant Syk inhibitory activities, with ZAP-70 inhibition. Representative compounds 10d and 11 not only exhibited strong inhibition of both Syk and ZAP-70 kinase but also suppressed IL-2 production by peripheral blood mononuclear cells and whole blood. (C) 2008 Elsevier Ltd. All rights reserved.