Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595333 | Bioorganic & Medicinal Chemistry Letters | 2012 | 8 Pages |
Abstract
Based on pharmacophore elucidation and docking studies on interactions of benzylidene anabaseine analogs with AChBPs and α7 nAChR, novel spirodiazepine and spiroimidazoline quinuclidine series have been designed. Binding studies revealed that some of hydrogen-bond donor containing compounds exhibit improved affinity and selectivity for the α7 nAChR subtype in comparison with most potent metabolite of GTS-21, 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine. Hydrophobicity and rigidity of the ligand also contribute into its binding affinity. We also describe alternative pharmacophoric features equidistant from the carbonyl oxygen atom of the conserved Trp-148 of the principal face, which may be exploited to further design diverse focused libraries targeting the α7 nAChR.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
David C. Kombo, Anatoly A. Mazurov, Joseph Chewning, Philip S. Hammond, Kartik Tallapragada, Terry A. Hauser, Jason Speake, Daniel Yohannes, William S. Caldwell,