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Bioorg Med Chem Lett. 2011 Nov 15;21(22):6714-23. doi: 10.1016/j.bmcl.2011.09.046. Epub 2011 Sep 21.

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

Author information

1
College of Pharmacy, Qatar University, PO Box 2713, Doha, Qatar. oghoneim@sjc.edu

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.

PMID:
21982496
PMCID:
PMC4104666
DOI:
10.1016/j.bmcl.2011.09.046
[Indexed for MEDLINE]
Free PMC Article

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