Computer aided fragment-based lead discovery has been successfully applied to the design of inhibitors of aspartyl protease enzyme β-secretase（BACE1）.A benzimidamide fragment,which binds to the two catalytic aspart...Computer aided fragment-based lead discovery has been successfully applied to the design of inhibitors of aspartyl protease enzyme β-secretase（BACE1）.A benzimidamide fragment,which binds to the two catalytic aspartic acid residues in the active site of the enzyme,was selected as the starting compound.A novel series of 3-phenethylbenzimidamide inhibitors were designed and synthesized.Although biological evaluation results showed that the compounds displayed poor inhibitory activity towards BACE1,3-phenethylbenzimidamide analogs might be modified as potential BACE1 inhibitors.展开更多
基金National Natural Science Foundation of China(Grant No. 21002002)Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 200800011057)
文摘Computer aided fragment-based lead discovery has been successfully applied to the design of inhibitors of aspartyl protease enzyme β-secretase（BACE1）.A benzimidamide fragment,which binds to the two catalytic aspartic acid residues in the active site of the enzyme,was selected as the starting compound.A novel series of 3-phenethylbenzimidamide inhibitors were designed and synthesized.Although biological evaluation results showed that the compounds displayed poor inhibitory activity towards BACE1,3-phenethylbenzimidamide analogs might be modified as potential BACE1 inhibitors.
