76539-34-9Relevant academic research and scientific papers
Synthesis, and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors
Zhu, Wufu,Wang, Wenhui,Xu, Shan,Wang, Jianqiang,Tang, Qidong,Wu, Chunjiang,Zhao, Yanfang,Zheng, Pengwu
, p. 1749 - 1756 (2016/04/05)
Four series of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (14a-e, 15a-g, 16a-e and 17a-g) were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Four selected compounds (15e, 16a-b and 17a) were further evaluated for the activity against c-Met kinase, HepG2 and Hela cell lines. Most of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 valuables in single-digit μM to nanomole range. Eleven of them are equal to more active than positive control Foretinib against one or more cell lines. The most promising compound 15e showed superior activity to Foretinib against A549, PC-3 and MCF-7 cell lines, with the IC50 values of 0.14 ± 0.08 μM, 0.24 ± 0.07 μM and 0.02 ± 0.01 μM, which were 4.6, 1.6 and 473.5 times more active than Foretinib (0.64 ± 0.26 μM, 0.39 ± 0.11 μM, 9.47 ± 0.22 μM), respectively. Structure-activity relationships (SARs) and docking studies indicated that the replacement of phenylpicolinamide scaffold with phenylpyrimidine fragment of the target compounds was benefit for the activity. What's more, the introduction of fluoro atom to the aminophenoxy part played no significant impact on the activity and any substituent group on aryl group is unfavourable for the activity.
Synthesis, activity and docking studies of phenylpyrimidine–carboxamide Sorafenib derivatives
Wang, Wenhui,Wu, Chunjiang,Wang, Jianqiang,Luo, Rong,Wang, Caolin,Liu, Xiaobo,Li, Jiqing,Zhu, Wufu,Zheng, Pengwu
, p. 6166 - 6173 (2016/12/06)
Two series of Sorafenib derivatives bearing phenylpyrimidine–carboxamide moiety (16a–g and 17a–p) were designed, synthesized and evaluated for the IC50values against three cancer cell lines (A549, MCF-7 and PC-3). Two selected compounds (17f and 17n) were further evaluated for the activity against VEGFR2/KDR kinase. More than half of the synthesized compounds showed moderate to excellent activity against three cancer cell lines. Compound 17f showed equal activity to Sorafenib against MCF-7 cell line, with the IC50values of 6.35 ± 0.43 μM. Meanwhile, compound 17n revealed more active than Sorafenib against A549 cell line, with the IC50values of 3.39 ± 0.37 μM. Structure–activity relationships (SARs) and docking studies indicated that the second series (17a–p) showed more active than the first series (16a–g). What's more, the introduction of fluoro atom to the phenoxy part played no significant impact on activity. In addition, the presence of electron-donating on aryl group was benefit for the activity.
