Optimization of (Arylpiperazinylbutyl)oxindoles Exhibiting Selective 5-HT(7) Receptor Antagonist Activity

Volk, Balázs ✉ [Volk, Balázs (Hatóanyag gyártóe...), author] Egis Pharmaceuticals Ltd.; Gacsályi, István [Gacsályi, István (farmakológia), author] Egis Pharmaceuticals Ltd.; Pallagi, Katalin; Poszávácz, László [Poszávácz, László (Szerves kémia), author] Egis Pharmaceuticals Ltd.; Gyönös, Ildikó; Szabó, Éva; Bakó, Tibor; Spedding, M; Simig, Gyula [Simig, Gyula (Gyógyszerkémia), author] Egis Pharmaceuticals Ltd.; Szénási, Gábor ✉ [Szénási, Gábor (kórélettan), author] Egis Pharmaceuticals Ltd.

English Article (Journal Article) Scientific
Published: JOURNAL OF MEDICINAL CHEMISTRY 0022-2623 1520-4804 54 (19) pp. 6657-6669 2011
  • SJR Scopus - Drug Discovery: D1
Subjects:
  • Basic medicine
  • Biological sciences
  • Pharmaceutical chemistry
  • Heterocyclic chemistry
  • Synthetic Organic chemistry
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 alpha(1)-adrenoceptor. Several derivatives exhibited high 5-HT(7)/5-HT(1A) selectivity, and the key structural factors for reducing undesired alpha(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.
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2025-02-19 13:22