title: 1-Thia-4,7-diaza-spiro[4.4]nonane-3,6-dione: a structural motif for 5-hydroxytryptamine 6 receptor antagonism.
abstract: A series of potent 5-hydroxytryptamine 6 (5-HT₆) receptor antagonists based on 1-thia-4,7-diaza-spiro[4.4]nonane-3,6-dione motif has been disclosed. Enantiomers of potent racemate compound 8a (K(i) = 26 nM) displayed difference in activity (K(i) of 15 nM versus 855 nM) signaling the influence of the stereochemistry of the chiral center on potency. In addition, the potent enantiomer displayed significant selectivity in biological activities over several related family members.
authors.affiliation: Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA, 19380-4245, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Hostetler
authors.forename: Derek
authors.initials: D
authors.lastname: Dunn
authors.forename: Beth A
authors.initials: BA
authors.lastname: McKenna
authors.forename: Karla
authors.initials: K
authors.lastname: Kopec
authors.forename: Sankar
authors.initials: S
authors.lastname: Chatterjee
mesh_terms: D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D053778:Thiazolidines / Q000737:chemistry*
chemical_list: D001552:Benzazepines; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; D053778:Thiazolidines; C097216:serotonin 6 receptor
keywords: 5-HT6 receptor; CNS disorders; antagonist