Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo［2, 3-d］pyrimidine derivatives

LIU Xiaofei; WANG Tingfang; JU Caoyun; ZHANG Can

doi:10.11665/j.issn.1000-5048.20170204

Journal of China Pharmaceutical University > 2017 > 48(2): 150-156. > DOI: 10.11665/j.issn.1000-5048.20170204

LIU Xiaofei, WANG Tingfang, JU Caoyun, ZHANG Can. Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo［2, 3-d］pyrimidine derivatives[J]. Journal of China Pharmaceutical University, 2017, 48(2): 150-156. DOI: 10.11665/j.issn.1000-5048.20170204

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Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo［2, 3-d］pyrimidine derivatives

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A series of 4-phenyl-pyrrolo［2, 3-d］pyrimidine derivatives were synthesized through modifying the structure of the lead compound ruxolitinib by molecular hybridization strategy. It was synthesized from pyrimidine-4, 6-diol by Vilsmeier-Haack reaction, S_NAr reaction, cyclized, dehydration, Suzuki coupling and finally acylated to give 12 new compounds( 12a - 12l ). All structures of the synthesized compounds were confirmed by ¹H NMR, ¹³C NMR, and HRMS analysis. The biological activities were evaluated in vitro. Their JAK2 inhibitory activities were studied using JAK2 enzymatic and TF1-GMCSF cellular assays. The results indicated that compounds 12b , 12e and 12h showed moderate activity. The anti-tumor activities were studied against JAK2-independent A549 cell line by the MTT assay. Results showed that the title compounds exhibited potent antiproliferative effect on A549, especially compound 12c (IC₅₀=0. 12 μmol/L), suggesting that this series compounds might be promising anti-tumor agents for futher investigation.
- myeloproliferative neoplasms(MPNs),
- JAK2 inhibitors,
- pyrrolo［2,3-d］pyrimidine,
- synthesis

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Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo［2, 3-d］pyrimidine derivatives

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