New serotonin 5-HT6 ligands from common feature pharmacophore hypotheses

Hye Jung Kim, Munikumar Reddy Doddareddy, Hyunah Choo, Yong Seo Cho, Kyoung Tai No, Woo Kyu Park, Ae Nim Pae

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44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalJournal of Chemical Information and Modeling
Volume48
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

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    Kim, H. J., Doddareddy, M. R., Choo, H., Cho, Y. S., No, K. T., Park, W. K., & Pae, A. N. (2008). New serotonin 5-HT6 ligands from common feature pharmacophore hypotheses. Journal of Chemical Information and Modeling, 48(1), 197-206. https://doi.org/10.1021/ci700160t