站内搜索
最新录用更多>>
4-(3-磺酰基苯基)氨基-6-甲酰基吡咯并[2,3-d]嘧啶类化合物的设计、合成与生物活性研究
投稿时间:2017-04-09  修订日期:2017-05-10  点此下载全文
引用本文:
摘要点击次数: 130
全文下载次数: 
作者单位E-mail
乔佳男 中国药科大学 764579493@qq.com 
王庭芳 中国药科大学 wtf66@126.com 
张灿 中国药科大学 zhangcan@cpu.edu.cn 
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
中文摘要:JAK2作为一种蛋白酪氨酸激酶,在造血系统中发挥关键作用,已成为骨髓增殖性肿瘤治疗中具有吸引力的药物靶点。本文以JAK2抑制剂Baricitinib和Fedratinib为先导,运用分子杂交药物设计原理,设计并合成了19个以4-(3-磺酰基苯基)氨基-6-甲酰基吡咯并[2,3-d]嘧啶(3)为母核、结构新颖的目标化合物。并通过JAK2激酶和粒细胞-巨噬细胞集落刺激因子(Granulocyte macrophage colony stimulating factor,GM-CSF)诱导的TF-1细胞对所合成的化合物进行了活性测试。结果显示,多数化合物具有JAK2抑制活性,其中化合物(31)表现出较好的JAK2激酶活性(IC50 = 0.009 μM)和GM-CSF诱导的TF-1细胞抑制活性(IC50 = 0.136 μM),表明该化合物具有潜在的研发价值。
中文关键词:磺酰基  吡咯并嘧啶  JAK2抑制剂  合成
 
Design, Synthesis and Bioactivity of 4- (3-sulfonylbenzene) amino-6-formylpyrrole [2,3-d] pyrimidine derivatives
Abstract:JAK2, as a cytoplasmic tyrosine kinase, plays a key role in the hematopoietic system and has become an attractive drug target for the treatment of myeloproliferative tumors. We used the JAK2 inhibitor Baricitinib and Fedratinib as the lead, and designed the novel 4- (3-sulfonylbenzene) amino-6-formylpyrrole [2,3-d] pyrimidine JAK2 inhibitors nucleus using the molecular hybrid drug design principle. 19 target compounds were synthesized by derivatization of sulfonyl and formyl groups respectively. We used JAK2 kinase and GM-CSF-induced TF-1 cells to measure the activities of compounds. The results showed that most compounds had JAK2 inhibitory activities. Among them, compound 31 had excellent inhibitory activity on JAK2 kinase ( IC50 = 0.009 μM ) and GM-CSF-induced TF-1 cells (IC50 = 0.136 μM), which proved that the compound had potential research and development value.
keywords:Sulfonyl  Pyrrolopyrimidine  JAK2 inhibitors  Synthesis
  查看/发表评论  下载PDF阅读器
分享按钮