期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 59, 期 24, 页码 11171-11181出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01506
关键词
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The design and synthesis of a series of quinuclidine-containing spirooxazolidines (spiroimidates) and their utility as alpha 7 nicotinic acaylcholine receptor partial agonists are described. Selected members of the series demonstrated excellent selectivity for alpha 7 over the highly homologous 5-HT3A receptor. Modification of the N-spiroirnidate heterocycle substituent led to (13,2R,4S)-N-isoquinolin-3-yl)-4'H-4-azaspirci[bicyclo [2.2.2] octane-2,5'oxazol]-2'-aynine (BMS-902483), a potent alpha 7 partial agonist, which improved cognition in preclinical rodent models.
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