Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R antagonists for the treatment of depression
- Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R antagonists for the treatment of depression
- 김영재; 태진성; 이강호; 임혜원; 추일한; 조희영; 박우규; 금교창; 추현아
- serotonin receptor; 5-HT7R; antagonist; depression; antidepressant
- Issue Date
- Bioorganic & medicinal chemistry
- VOL 22, NO 17, 4587-4596
- 5-HT7 receptor (5-HT7R) is a promising target for the treatment of depression and neuropathic pain. 5-HT7R antagonists exhibited antidepressant effects, while the agonists produced strong anti-hyperalgesic effects. In our efforts to discover selective 5-HT7R antagonists or agonists, N-biphenylylmethyl 2-methoxyphenylpiperazinylalkanamides 1 were designed, synthesized, and biologically evaluated against 5-HT7R. Among the synthesized compounds, N-2′-chlorobiphenylylmethyl 2-methoxyphenylpiperazinylpentanamide 1–8 showed the best binding affinity with a Ki value of 8.69 nM and it was verified as a novel antagonist according to functional assays. The compound 1–8 was very selective over 5-HT1DR, 5-HT2AR, 5-HT3R, 5-HT5AR and 5-HT6R and moderately selective over 5-HT1AR, 5-HT1BR and 5-HT2CR. The novel 5-HT7R antagonist 1–8 exhibited an antidepressant effect at a dose of 25 mg/kg in the forced swimming test in mice and showed a U-shaped dose–response curve which typically appears in 5-HT7R antagonists such as SB-269970 and lurasidone.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.