Novel N-acyl-carbazole derivatives as 5-HT7R antagonists

Title
Novel N-acyl-carbazole derivatives as 5-HT7R antagonists
Authors
임혜원추현아김영재염미영태진성
Keywords
5-HT7R; antagonist; N-acyl-carbazole; serotonin; depression; GPCR
Issue Date
2016-03
Publisher
European journal of medicinal chemistry
Citation
VOL 110, 302-310
Abstract
To discover a novel 5-HT7R antagonist for treatment of depression, we designed N-acyl-carbazole derivatives which were synthesized and biologically evaluated against 5-HT7R. Among total 30 compounds synthesized, four compounds 27-30 showed good binding affinities with K-i values of <100 nM. The compound 28, 1-(9H-carbazol-9-yl)-6-(4-(2-methoxyphenyl)piperazin-1-yl)hexan-1-one, showed good selectivity over other serotonin receptor subtypes and turned out to be a novel selective 5-HT7R antagonist following functional assays. The compound 28 showed moderate activity on hERG channel and good stability in microsomal stability test. The compound 28 exhibited a good pharmacokinetic profile with 67.8% oral bioavailability and good penetration to the brain. The compound 28 was also tested in in vivo depression animal model and showed antidepressant effect in the forced swimming test. Therefore, the selective 5-HT7R antagonist 28 can be considered as a good lead for discovery of novel 5HT(7)R antagonists as antidepressants.
URI
http://pubs.kist.re.kr/handle/201004/59079
ISSN
02235234
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE