Discovery and Structure−Activity Relationship of Quinuclidine Benzamides as Agonists of α7 Nicotinic Acetylcholine Receptors

Autor:	Raymond S. Hurst, Vincent E. Groppi, Bruce N. Rogers, Alice L. Bodnar, Theron M. Wall, Luz A. Cortes-Burgos, Jason K. Myers, Dac M. Dinh, Nicole R. Higdon, Mark L. Wolfe, Erik H. F. Wong, Karen K. Cook, Mihály Hajós, William E. Hoffmann
Rok vydání:	2005
Předmět:	Agonist Quinuclidines Patch-Clamp Techniques alpha7 Nicotinic Acetylcholine Receptor medicine.drug_class Gating Receptors Nicotinic Pharmacology Hippocampus complex mixtures Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Ganglion type nicotinic receptor Drug Discovery medicine Animals Combinatorial Chemistry Techniques Structure–activity relationship Nicotinic Agonists Receptor Cells Cultured Acetylcholine receptor Neurons Serotonin 5-HT3 Receptor Agonists Stereoisomerism Rats Nicotinic agonist nervous system chemistry Biochemistry Benzamides Molecular Medicine Ion Channel Gating psychological phenomena and processes Quinuclidine
Zdroj:	Journal of Medicinal Chemistry. 48:905-908
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm049363q
Popis:	A library of benzamides was tested for alpha7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have alpha7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT(3) receptor, a structural homologue of the alpha7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native alpha7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c869cd816f6b43ca88a5152d5473990d https://doi.org/10.1021/jm049363q Zobrazit plný text záznamu