Bioorganic & Medicinal Chemistry Letters 2005-11-15

3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation.

Jotham W Coe, Paige R Brooks, Michael C Wirtz, Crystal G Bashore, Krista E Bianco, Michael G Vetelino, Eric P Arnold, Lorraine A Lebel, Carol B Fox, F David Tingley, David W Schulz, Thomas I Davis, Steven B Sands, Robert S Mansbach, Hans Rollema, Brian T O'Neill

Index: Bioorg. Med. Chem. Lett. 15 , 4889-97, (2005)

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Abstract

3,5-Bicyclic aryl piperidines are a new class of high-affinity alpha4beta2 nicotinic receptor agents. We have sought nicotinic receptor partial agonists of the alpha4beta2 nicotinic acetylcholine receptor for smoking cessation, and a number of compounds fulfill potency, selectivity, and efficacy requirements in vitro. In vivo, selected agents demonstrate potent partial agonist efficacy on the mesolimbic dopamine system, a key measure of therapeutic potential for smoking cessation.