Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo[2, 3-d] pyrimidine derivatives
10.11665/j.issn.1000-5048.20170204
- VernacularTitle:4-苯基-吡咯并[2,3-d]嘧啶类JAK2激酶抑制剂的设计、合成和抗肿瘤活性
- Author:
Xiaofei LIU
;
Tingfang WANG
;
Caoyun JU
;
Can ZHANG
- Keywords:
myeloproliferative neoplasms (MPNs);
JAK2 inhibitors;
pyrrolo[2,3-d] pyrimidine;
synthesis
- From:
Journal of China Pharmaceutical University
2017;48(2):150-156
- CountryChina
- Language:Chinese
-
Abstract:
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,SNAr reaction,cyclized,dehydration,Suzuki coupling and finally acylated to give 12 new compounds(12a-121).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 tide 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.
