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, Gábor Szénási

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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
Issue number19
Publication statusPublished - Oct 13 2011


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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, 54(19), 6657-6669. https://doi.org/10.1021/jm200547z