Abstract：
:Serotonin 5-HT6 receptor antagonists are thought to play an important role in the treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel and potent 5-HT6 antagonists and to provide a new idea for drug design, we used a ligand-based pharmacophore to perform the virtual screening of a commercially available database. A three-dimensional common feature pharmacophore model was developed by using the HipHop program provided in Catalyst software and was used as a query for screening the database. A recursive partitioning (RP) model which can separate active and inactive compounds was used as a filtering system. Finally a sequential virtual screening procedure (SQSP) was conducted, wherein both the common feature pharmacophore and the RP model were used in succession to improve the results. Some of the hits were selected based on druglikeness, ADME properties, structural diversity, and synthetic accessibility for real biological evaluation. The best hit compound showed a significant IC50 value of 9.6 nM and can be used as a lead for further drug development.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Kim HJ,Doddareddy MR,Choo H,Cho YS,No KT,Park WK,Pae ANdoi
10.1021/ci700160tsubject
Has Abstractpub_date
2008-01-01 00:00:00pages
197-206issue
1eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
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