(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor
| Autor: | James J. Napier, Jack Gordon, Eifion Phillips, John Zongrone, David Gurley, Yanyi Zhu, Thomas DeCory, James T. Loch, Ronald Griffith, Alexander Kover, Michael Balestra, Anthony Sampognaro, George B. Mullen, and Alan Rosen, Patrick Verhoest, James Blosser, Robert J. Murray, Anthony Machulskis, Gregory Hale, Robert A. Mack, John Macor, Ed Wu |
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| Rok vydání: | 2000 |
| Předmět: |
Agonist
Bridged-Ring Compounds alpha7 Nicotinic Acetylcholine Receptor medicine.drug_class Stereochemistry Xenopus In Vitro Techniques Receptors Nicotinic Hippocampus Radioligand Assay Structure-Activity Relationship Ganglion type nicotinic receptor Prosencephalon Drug Discovery Muscarinic acetylcholine receptor M5 medicine Enzyme-linked receptor Animals Spiro Compounds Nicotinic Agonists Acetylcholine receptor Chemistry Stereoisomerism Acetylcholine Rats Nicotinic agonist Oocytes Molecular Medicine Alpha-4 beta-2 nicotinic receptor medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 43(22) |
| ISSN: | 0022-2623 |
| Popis: | Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity. |
| Databáze: | OpenAIRE |
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