Structure-activity studies of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes: a novel class of highly potent nicotinic receptor ligands.

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Breining SR, Melvin M, Bhatti BS, Byrd GD, Kiser MN, Hepler CD, Hooker DN, Zhang J, Reynolds LA, Benson LR, Fedorov NB, Sidach SS, Mitchener JP, Lucero LM, Lukas RJ, Whiteaker P, Yohannes D

Structure-activity studies of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes: a novel class of highly potent nicotinic receptor ligands.

J Med Chem. 2012 Nov 26;55(22):9929-45. doi: 10.1021/jm3011299. Epub 2012 Oct 17.

PubMed ID

23025891 [ View in PubMed

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Abstract

The potential for nicotinic ligands with affinity for the alpha4beta2 or alpha7 subtypes to treat such diverse diseases as nicotine addiction, neuropathic pain, and neurodegenerative and cognitive disorders has been exhibited clinically for several compounds while preclinical activity in relevant in vivo models has been demonstrated for many more. For several therapeutic programs, we sought nicotinic ligands with various combinations of affinity and function across both subtypes, with an emphasis on dual alpha4beta2-alpha7 ligands, to explore the possibility of synergistic effects. We report here the structure-activity relationships (SAR) for a novel series of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes and characterize many of the analogues for activity at multiple nicotinic subtypes.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rivanicline	Neuronal acetylcholine receptor subunit beta-2	Ki (nM)	26	N/A	N/A	Details