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

被引：7
作者：
Ghoneim, Ola M. [1 ]
Ibrahim, Diaa A. [2 ]
El-Deeb, Ibrahim M. [3 ]
Lee, So Ha [3 ]
Booth, Raymond G. [4 ]
机构：
[1] Qatar Univ, Coll Pharm, Doha, Qatar
[2] Natl Org Drug Control & Res, Giza 112311, Egypt
[3] Korea Inst Sci & Technol, Life Hlth Div, Seoul 130650, South Korea
[4] Univ Florida, Coll Pharm, Gainesville, FL 32610 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 22期
关键词：
Autism; Selective Serotonin Reuptake Inhibitors (SSRIs); Pharmacophore; SEROTONIN REUPTAKE INHIBITORS; BIOLOGICAL EVALUATION; RECEPTOR; DERIVATIVES; ANTAGONISTS; PIPERAZINES; DISRUPTION; ACTIVATION;
D O I：
10.1016/j.bmcl.2011.09.046
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6714 / 6723
页数：10
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