Design, synthesis and bioactivities of 4-(3-sulfonylbenzene)amino-6-formylpyrrole［2, 3-d］ pyrimidine derivatives

QIAO Jianan; WANG Tingfang; ZHANG Can

doi:10.11665/j.issn.1000-5048.20170508

Journal of China Pharmaceutical University > 2017 > 48(5): 554-562. > DOI: 10.11665/j.issn.1000-5048.20170508

QIAO Jianan, WANG Tingfang, ZHANG Can. Design, synthesis and bioactivities of 4-(3-sulfonylbenzene)amino-6-formylpyrrole［2, 3-d］ pyrimidine derivatives[J]. Journal of China Pharmaceutical University, 2017, 48(5): 554-562. DOI: 10.11665/j.issn.1000-5048.20170508

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Design, synthesis and bioactivities of 4-(3-sulfonylbenzene)amino-6-formylpyrrole［2, 3-d］ pyrimidine derivatives

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Taking JAK2 inhibitor baricitinib and fedratinib as the lead compounds, to design the novel 4-(3-sulfonylbenzene)amino-6-formylpyrrole［2, 3-d］ pyrimidine JAK2 inhibitors nucleus using the molecular hybrid drug design principle. 17 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 μmol/L )and GM-CSF-induced TF-1 cells(IC₅₀=0. 136 μmol/L), which proved that the compound had potential research and development value.
- sulfonyl,
- pyrrolopyrimidine,
- JAK2 inhibitors,
- synthesis,
- bioactivity

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Design, synthesis and bioactivities of 4-(3-sulfonylbenzene)amino-6-formylpyrrole［2, 3-d］ pyrimidine derivatives

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