Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370242 | Bioorganic & Medicinal Chemistry Letters | 2011 | 10 Pages |
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 5HT1B/1D autoreceptors antagonists motivated us to incorporate SSRIs and 5HT1B/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 (Ki = 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.
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