Ghoneim, Ola M. Ibrahim, Diaa A. El-Deeb, Ibrahim M. Lee, So Ha Booth, Raymond G. 2024-01-20T16:01:50Z 2024-01-20T16:01:50Z 2021-09-04 2011-11-15 0960-894X https://pubs.kist.re.kr/handle/201004/129806 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. (C) 2011 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. SEROTONIN REUPTAKE INHIBITORS BIOLOGICAL EVALUATION RECEPTOR DERIVATIVES ANTAGONISTS PIPERAZINES DISRUPTION ACTIVATION A novel potential therapeutic avenue for autism: Design, synthesis and pharmacophore generation of SSRIs with dual action Article 10.1016/j.bmcl.2011.09.046 1 Bioorganic & Medicinal Chemistry Letters, v.21, no.22, pp.6714 - 6723 Bioorganic & Medicinal Chemistry Letters 21 22 6714 6723 scie scopus 000296423700016 2-s2.0-80054765578 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article SEROTONIN REUPTAKE INHIBITORS BIOLOGICAL EVALUATION RECEPTOR DERIVATIVES ANTAGONISTS PIPERAZINES DISRUPTION ACTIVATION Autism Selective Serotonin Reuptake Inhibitors (SSRIs) Pharmacophore