A series of benzohydrazide derivatives as novel ribosomal S6 kinase 2 （RSK2） inhibitors were designed and synthesized from a hit compound previously discovered by ligand-based virtual screening. Biological assays sh...A series of benzohydrazide derivatives as novel ribosomal S6 kinase 2 （RSK2） inhibitors were designed and synthesized from a hit compound previously discovered by ligand-based virtual screening. Biological assays showed that these compounds possessed moderate inhibitory activities towards RSK2. The structural activity relationships （SAR） were elucidated by molecular docking and further optimization was performed.展开更多
A series of triazole and benzotriazole derivatives as novel p90 ribosomal S6 protein kinase 2 （RSK2） inhibitors were designed and synthesized. The in vitro activities against RSK2 were evaluated, and among 14 compou...A series of triazole and benzotriazole derivatives as novel p90 ribosomal S6 protein kinase 2 （RSK2） inhibitors were designed and synthesized. The in vitro activities against RSK2 were evaluated, and among 14 compounds, compounds 5, 6, 11, 12, 13 and 14 exhibited enzyme IC50 values of 8.91, 2.86, 3.19, 3.05, 4.49 and 2.09 μmol/L re- spectively. The proposed binding modes were simulated using molecular docking method, and the docking results coupled with the stmcture-activi1：y relationship （SAR） analysis indicated that all these active compounds bound to the RSK2 ATP binding site at NTKD, and the electron-donating groups on the 4-position of phenyl were the deter- minant point for the inhibitory activity.展开更多
基金The Fundamental Research Funds for the Central Universitiesthe National Natural Science Foundation of China(Grants No.21173076,81102375and81102420)+3 种基金the Specialized Research Fund for the Doctoral Program of Higher Education of China(Grants No.20090074120012 and 20110074120009)the Shanghai Committee of Science and Technology(Grants No.11DZ2260600 and 10431902600)the Innovation Program of Shanghai Municipal Education Commission(Grant No.10ZZ41)the 863 Hi-Tech Program of China(Grant No.2012AA020308)
文摘A series of benzohydrazide derivatives as novel ribosomal S6 kinase 2 （RSK2） inhibitors were designed and synthesized from a hit compound previously discovered by ligand-based virtual screening. Biological assays showed that these compounds possessed moderate inhibitory activities towards RSK2. The structural activity relationships （SAR） were elucidated by molecular docking and further optimization was performed.
基金The research is supported in part by the Fundamental Research Funds for the Central Universities,the National Natural Science Foundation of China，the Shanghai Committee of Science and Technology
文摘A series of triazole and benzotriazole derivatives as novel p90 ribosomal S6 protein kinase 2 （RSK2） inhibitors were designed and synthesized. The in vitro activities against RSK2 were evaluated, and among 14 compounds, compounds 5, 6, 11, 12, 13 and 14 exhibited enzyme IC50 values of 8.91, 2.86, 3.19, 3.05, 4.49 and 2.09 μmol/L re- spectively. The proposed binding modes were simulated using molecular docking method, and the docking results coupled with the stmcture-activi1：y relationship （SAR） analysis indicated that all these active compounds bound to the RSK2 ATP binding site at NTKD, and the electron-donating groups on the 4-position of phenyl were the deter- minant point for the inhibitory activity.
