Synthesis and Biological Evaluation of Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT sub(1A) Antagonists: The Discovery of Lecozotan

Synthesis and Biological Evaluation of Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT sub(1A) Antagonists: The Discovery of Lecozotan

A series of benzodioxanylpiperazine derivatives possessing a 4-aryl amide substituent was prepared and evaluated for 5-HT sub(1A) affinity and functional antagonist activity in vitro and in vivo. All of the compounds in this series possessed high affinity for the human 5-HT sub(1A) receptor and many...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of medicinal chemistry 2005-05, Vol.48 (10), p.3467-3470
Hauptverfasser: Childers, WE Jr, Abou-Gharbia, MA, Kelly, M G, Andree, TH, Harrison, B L, Ho, D M, Hornby, G, Huryn, D M, Potestio, L, Rosenzweig-Lipson, S J, Schmid, J, Smith, D L, Sukoff, S J, Zhang, G, Schechter, LE
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:A series of benzodioxanylpiperazine derivatives possessing a 4-aryl amide substituent was prepared and evaluated for 5-HT sub(1A) affinity and functional antagonist activity in vitro and in vivo. All of the compounds in this series possessed high affinity for the human 5-HT sub(1A) receptor and many displayed potent antagonist activity in vitro and varying degrees of intrinsic activity in vivo. Compound 11c (Lecozotan) was selected for further development and is currently in clinical trials.
ISSN:0022-2623
DOI:10.1021/jm049493z