High Activity Lead Compounds Derivation And Performance Research

Based on the ligand-based virtual screening program SHAFTS and structure-based virtual screening protocols, some lead compounds with potent inhibitory activities against RSK2 and IGF-1R were discovered. Three series of derivatives with different scaffolds were designed and synthesized. Their spectral characteristics, antitumor potency, pesticide activity were evaluated.The first series based on 5-arylidene-2-thiothiazolidinone scaffold were designed and synthesized. The structural optimization was focused on different number of substituents at different position of phenyl to occupy the hydrophobic pocket. Among them 53 compounds have not been reported before.The second series based on phenyl-N-(4H-1,2,4-triazol-4-yl)methanimine scaffold was designed and 17 compounds were synthesized focused on the different substituents on phenyl. Some compounds showed potent inhibition against RSK2, compound B19 and B21 exhibited the most potent inhibition against RSK2 with an IC50 value of 8.9μM and 2.86μM.The third series based on 4-amine-2-(benzo[d]oxazol-2-yl) phenol scaffold were designed and synthesized. Hydrophilic and hydrophobic substituents were introduced onto the phenyl to improve the activity against RSK2.Some of three series of compounds showed potent insecticidal, fungicidal and herbicidal activity with novel scaffolds as plant protector. Three compounds (A18,A34,A46) exhibited moderate inhibitory activity against Amaranthus, which might deserve to further studied.