A novel potential therapeutic avenue for autism: Design, synthesis and pharmacophore generation of SSRIs with dual action

作者:Ghoneim Ola M*; Ibrahim Diaa A; El Deeb Ibrahim M; Lee So Ha; Booth Raymond G
来源:Bioorganic & Medicinal Chemistry Letters, 2011, 21(22): 6714-6723.
DOI:10.1016/j.bmcl.2011.09.046

摘要

Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one 'hybrid' molecule. A library of virtual 'hybrid' molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i) = 0.013-5000 nM) and used as 3D query. Compounds with fit values (>= 2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.

  • 出版日期2011-11-15