In:
ChemMedChem, Wiley, Vol. 8, No. 11 ( 2013-11), p. 1855-1864
Abstract:
The 5‐HT 7 receptor (5‐HT 7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5‐HT 7 R antagonist SB‐269970 exhibited antidepressant‐like activity, whereas systemic administration of the 5‐HT 7 R agonist AS‐19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5‐HT 7 R antagonists or agonists, aryl biphenyl‐3‐ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5‐HT 7 R. 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‐HT 7 R (p K i =7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5‐HT 7 R over other serotonin receptor subtypes, such as 5‐HT 1 R, 5‐HT 2 R, 5‐HT 3 R, and 5‐HT 6 R. 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.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201300240
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2209649-8
SSG:
15,3
Permalink