Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT 7 receptor antagonist activity

Balázs Volk, István Gacsályi, Katalin Pallagi, László Poszávácz, Ildikó Gyönös, Éva Szabó, Tibor Bakó, Michael Spedding, Gyula Simig, G. Szénási

Research output: Article

32 Citations (Scopus)

Abstract

A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT 7 receptor antagonists has been studied for their selectivity toward the 5-HT 1A receptor and α 1-adrenoceptor. Several derivatives exhibited high 5-HT 7/5-HT 1A selectivity, and the key structural factors for reducing undesired α 1-adrenergic receptor binding have also been identified. Rapid metabolism, a common problem within this family of compounds, could be circumvented with appropriate substitution patterns on the oxindole carbocycle. Contrary to expectations, none of the compounds produced an antidepressant-like action in the forced swimming test in mice despite sufficiently high brain concentrations. On the other hand, certain analogues showed significant anxiolytic activity in two different animal models: the Vogel conflict drinking test in rats and the light-dark test in mice.

Original languageEnglish
Pages (from-to)6657-6669
Number of pages13
JournalJournal of Medicinal Chemistry
Volume54
Issue number19
DOIs
Publication statusPublished - okt. 13 2011

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Serotonin Receptors
Adrenergic Receptors
Serotonin
Receptor, Serotonin, 5-HT1A
Anti-Anxiety Agents
Antidepressive Agents
Drinking
Animal Models
Light
Brain
oxindole

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT 7 receptor antagonist activity. / Volk, Balázs; Gacsályi, István; Pallagi, Katalin; Poszávácz, László; Gyönös, Ildikó; Szabó, Éva; Bakó, Tibor; Spedding, Michael; Simig, Gyula; Szénási, G.

In: Journal of Medicinal Chemistry, Vol. 54, No. 19, 13.10.2011, p. 6657-6669.

Research output: Article

Volk, B, Gacsályi, I, Pallagi, K, Poszávácz, L, Gyönös, I, Szabó, É, Bakó, T, Spedding, M, Simig, G & Szénási, G 2011, 'Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT 7 receptor antagonist activity', Journal of Medicinal Chemistry, vol. 54, no. 19, pp. 6657-6669. https://doi.org/10.1021/jm200547z
Volk, Balázs ; Gacsályi, István ; Pallagi, Katalin ; Poszávácz, László ; Gyönös, Ildikó ; Szabó, Éva ; Bakó, Tibor ; Spedding, Michael ; Simig, Gyula ; Szénási, G. / Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT 7 receptor antagonist activity. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 19. pp. 6657-6669.
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AU - Gyönös, Ildikó

AU - Szabó, Éva

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