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

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Edink E, Akdemir A, Jansen C, van Elk R, Zuiderveld O, de Kanter FJ, van Muijlwijk-Koezen JE, Smit AB, Leurs R, de Esch IJ

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

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1448-54. doi: 10.1016/j.bmcl.2011.12.008. Epub 2011 Dec 9.

PubMed ID

22243960 [ View in PubMed

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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 alpha7 and alpha4beta2 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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Nicotine	Neuronal acetylcholine receptor subunit beta-2	Ki (nM)	12.59	N/A	N/A	Details