Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 receptor antagonists

Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6nM in binding assay, IC50 of 15nM in functional cAMP antagonism assay) was separated into corresponding enantiomers...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2014-05, Vol.24 (9), p.2094-2097
Hauptverfasser:	Hostetler, Greg, Dunn, Derek, McKenna, Beth Ann, Kopec, Karla, Chatterjee, Sankar
Format:	Artikel
Sprache:	eng
Schlagworte:	5-Hydroxytryptamine Animals Antagonist Brain - metabolism CNS Humans Lactam Lactams - chemistry Lactams - pharmacokinetics Lactams - pharmacology Oxazolidinone Oxazolidinones - chemistry Oxazolidinones - pharmacokinetics Oxazolidinones - pharmacology Rats Receptors, Serotonin - metabolism Serotonin Antagonists - chemistry Serotonin Antagonists - pharmacokinetics Serotonin Antagonists - pharmacology
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Beschreibung
Zusammenfassung:	Lactam and oxazolidinone derived potent 5-hydroxytryptamine 6 (5-HT6) receptor antagonists have been disclosed. One potent member from the lactam series, racemic compound 14 (Ki of 2.6nM in binding assay, IC50 of 15nM in functional cAMP antagonism assay) was separated into corresponding enantiomers that displayed the effect of chirality on binding potency (Ki of 1.6nM and 3000nM, respectively). The potent enantiomer displayed an IC50 of 8nM in cAMP antagonism assay, selectivity against a number of family members as well as brain permeability in rats after 6h post oral administration.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2014.03.049