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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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2014-05, Vol.24 (9), p.2094-2097
Main Authors: Hostetler, Greg, Dunn, Derek, McKenna, Beth Ann, Kopec, Karla, Chatterjee, Sankar
Format: Article
Language:English
Subjects:
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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Summary: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