Preparation and characterization of N-(3-pyridinyl) spirocyclic diamines as ligands for nicotinic acetylcholine receptors.

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Sippy KB, Anderson DJ, Bunnelle WH, Hutchins CW, Schrimpf MR

Preparation and characterization of N-(3-pyridinyl) spirocyclic diamines as ligands for nicotinic acetylcholine receptors.

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1682-5. doi: 10.1016/j.bmcl.2009.01.099. Epub 2009 Feb 4.

PubMed ID

19232492 [ View in PubMed

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Abstract

Several N-pyridin-3-yl spirobicyclic diamines, designed as conformationally restricted analogs of tebanicline (ABT-594), were synthesized as novel ligands for nicotinic acetylcholine receptors (nAChR). The spirocyclic compounds exhibited weaker binding affinity, than other constrained analogs in accord with a pharmacophore model. Nevertheless, some (1a, 1b) possessed (partial) agonist potencies comparable to nicotine at the alpha4beta2 subtype, but with greatly improved selectivity relative to the alpha3beta4* nAChR.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Nicotine	Neuronal acetylcholine receptor subunit alpha-3	EC 50 (nM)	9400	N/A	N/A	Details
Nicotine	Neuronal acetylcholine receptor subunit alpha-4	EC 50 (nM)	4700	N/A	N/A	Details