Using rational drug design to develop atypical antipsychotic drug candidates, we generated novel and metabolically stable pyrrolobenzazepines with an optimized pKi 5-HT2A/O2 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
Novel Atypical Antipsychotic Agents: Rational Design, an Efficient Palladium-Catalyzed Route, and Pharmacological Studies / Campiani, G., Butini, S., Fattorusso, C., Trotta, F., Gemma, S., Catalanotti, B., Nacci, V., Fiorini, I., Cagnotto, A., Mereghetti, I., Mennini, T., Minetti, P., DI CESARE, M.A., Stasi, M.A., DI SERIO, S., Ghirardi, O., Tinti, O., Carminati, P.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 48:(2005), pp. 1705-1708. [10.1021/jm049629t]
Novel Atypical Antipsychotic Agents: Rational Design, an Efficient Palladium-Catalyzed Route, and Pharmacological Studies
FATTORUSSO, CATERINA;CATALANOTTI, BRUNO;
2005
Abstract
Using rational drug design to develop atypical antipsychotic drug candidates, we generated novel and metabolically stable pyrrolobenzazepines with an optimized pKi 5-HT2A/O2 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 candidateI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
