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An Updated Unified Pharmacophore Model of the Benzodiazepine Binding Site on γ-Aminobutyric Acida Receptors: Correlation with Comparative Models

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Abstract:

A successful unified pharmacophore/receptor model which has guided the synthesis of subtype selective compounds is reviewed in light of recent developments both in ligand synthesis and structural studies of the binding site itself. The evaluation of experimental data in combination with a comparative model of the α1β2γ2 GABAA receptor leads to an orientation of the pharmacophore model within the Bz BS. Results not only are important for the rational design of selective ligands, but also for the identification and evaluation of possible roles which specific residues may have within the benzodiazepine binding pocket.

Keywords: Aminobutyric acid(A) receptors; GABA-A; benzodiazepine; computer-assisted analysis; gated ion channels

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707782360097

Affiliations: Department of Chemistry, 3210 North Cramer Street, UW-Milwaukee, Chemistry Building Milwaukee, WI 53201, UWMilwaukee,Milwaukee, WI 53211, USA.

Publication date: November 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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