Rational design of a novel peripherally-restricted, orally active CB sub(1) cannabinoid antagonist containing a 2,3-diarylpyrrole motif

Rational design of a novel peripherally-restricted, orally active CB sub(1) cannabinoid antagonist containing a 2,3-diarylpyrrole motif

A new series of 2,3-diarylpyrroles have been prepared and evaluated as CB sub(1) antagonists. Modulation of the topological polar surface area allowed the identification of high affinity peripherally-restricted CB sub(1) antagonists. Compound 11, obtained after further optimization of the metabolic...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bioorganic & medicinal chemistry letters 2010-08, Vol.20 (15), p.4573-4577
Hauptverfasser: Hortala, Laurent, Rinaldi-Carmona, Murielle, Congy, Christian, Boulu, Laurent, Sadoun, Freddy, Fabre, Gerard, Finance, Olivier, Barth, Francis
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:A new series of 2,3-diarylpyrroles have been prepared and evaluated as CB sub(1) antagonists. Modulation of the topological polar surface area allowed the identification of high affinity peripherally-restricted CB sub(1) antagonists. Compound 11, obtained after further optimization of the metabolic profile displayed very low brain penetration, yet was able to reverse CP55940-induced gastrointestinal transit inhibition following oral administration.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2010.06.017