Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein

E.S. Edink, A. Akdemir, C.J.W. Jansen, R. van Elk, O.P. Zuiderveld, F.J.J. de Kanter, J.E. van Muijlwijk- Koezen, A.B. Smit, R. Leurs, I.J.P. de Esch

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the α7 and α4β2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes. © 2011 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1448-1454
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number3
DOIs
Publication statusPublished - 2012

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