Indentification of Pharmacophore Model, Synthesis and biological evaluation of N-phenyl-1-arylamide and N-phenylbenzenesulfonamide derivatives as BACE 1 inhibitors
The pharmacophore model of arylpiperazine amide derivatives was built using Discovery Studio 2.0 software package and the validition of the best pharmacophore model (Hypo 1) was ascertained by Enrichment and ROC method (EF at 2%, 5% and 10% are 30.6, 12.2 and 7.7; AUC of the ROC curve is 0.93). According to the estimated result, eleven N-phenyl-1-arylamide N-phenylbenzenesulfonamide derivatives 5-7,12a-g were selected, synthesized and determined their BACE 1 inhibitory activities experimentally. The theoretical results of them were in good agreement with the experimental values. Compound 12d, which displayed the highest BACE 1 activity (18.33±2.80μol/L) among these two series, was picked out to study the protein binding pattern and the result showed that 12d was in close contact with two essential catalytic aspartates (Asp32 and Asp228) of the BACE 1.
Pharmacophore model Alzheimers disease BACE 1 Non-peptidomimetic inhibitor
Wenhai Huang Haiping Yu Rong Sheng ia Li Yongzhou Hu
ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang University, Zijingang Campus, Hangzhou 310 The National Center for Drug Screening, Shanghai 201203, China
国际会议
广州
英文
431-451
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）