Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists

Jeeyeon Kim, Youngjae Kim, Jinsung Tae, Miyoung Yeom, Bongjin Moon, Xi Ping Huang, Bryan L. Roth, Kangho Lee, Hyewhon Rhim, I. C. Choo, Youhoon Chong, Gyochang Keum, Ghilsoo Nam, Hyunah Choo

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


The 5-HT7 receptor (5-HT7R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5- HT7R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7R agonist AS- 19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT 7R. Among the synthesized compounds, 1-([2′-methoxy- (1,1′-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7R (pKi=7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7R over other serotonin receptor subtypes, such as 5-HT1R, 5- HT2R, 5-HT 3R, and 5-HT6R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function.

Original languageEnglish
Pages (from-to)1855-1864
Number of pages10
Issue number11
Publication statusPublished - 2013 Nov

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry


Dive into the research topics of 'Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists'. Together they form a unique fingerprint.

Cite this