Novel Atypical Antipsychotic Agents:  Rational Design, an Efficient Palladium-Catalyzed Route, and Pharmacological Studies

Autor: Campiani, G., Butini, S., Fattorusso, C., Trotta, F., Gemma, S., Catalanotti, B., Nacci, V., Fiorini, I., Cagnotto, A., Mereghetti, I., Mennini, T., Minetti, P., Cesare, M. A. Di, Stasi, M. A., Serio, S. Di, Ghirardi, O., Tinti, O., Carminati, P.
Zdroj: Journal of Medicinal Chemistry; March 2005, Vol. 48 Issue: 6 p1705-1708, 4p
Abstrakt: Using rational drug design to develop atypical antipsychotic drug candidates, we generated novel and metabolically stable pyrrolobenzazepines with an optimized pKi 5-HT2A/D2 ratio. 5a, obtained by a new palladium-catalyzed three-step synthesis, was selected for further pharmacological and biochemical investigations and showed atypical antipsychotic properties in vivo. 5a was active on conditioned avoidance response at 0.56 mg/kg, it had low cataleptic potential and proved to be better than ST1899, clozapine, and olanzapine, representing a new clinical candidate.
Databáze: Supplemental Index