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

Youngjae Kim, Miyoung Yeom, Jinsung Tae, Hyewhon Rhim, Hyunah Choo

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 Ki 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 5-HT7R antagonists as antidepressants.

Original languageEnglish
Pages (from-to)302-310
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume110
DOIs
Publication statusPublished - 2016 Mar 3

Fingerprint

Antidepressive Agents
Derivatives
Pharmacokinetics
Serotonin Receptors
Biological Availability
Assays
Brain
Animals
Animal Models
carbazole
compound 30
Swimming
Lead

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Kim, Youngjae ; Yeom, Miyoung ; Tae, Jinsung ; Rhim, Hyewhon ; Choo, Hyunah. / Novel N-acyl-carbazole derivatives as 5-HT7R antagonists. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 110. pp. 302-310.
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Novel N-acyl-carbazole derivatives as 5-HT7R antagonists. / Kim, Youngjae; Yeom, Miyoung; Tae, Jinsung; Rhim, Hyewhon; Choo, Hyunah.

In: European Journal of Medicinal Chemistry, Vol. 110, 03.03.2016, p. 302-310.

Research output: Contribution to journalArticle

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