A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action.
Article Details
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Ghoneim OM, Ibrahim DA, El-Deeb IM, Lee SH, Booth RG
A novel potential therapeutic avenue for autism: design, synthesis and pharmacophore generation of SSRIs with dual action.
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6714-23. doi: 10.1016/j.bmcl.2011.09.046. Epub 2011 Sep 21.
- PubMed ID
- 21982496 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Ergotamine 5-hydroxytryptamine receptor 1B Ki (nM) 2.1 N/A N/A Details Ergotamine 5-hydroxytryptamine receptor 1D Ki (nM) 4.3 N/A N/A Details