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. © 2005 American Chemical Society.
Campiani, G., Butini, S., Fattorusso, C., Frotta, F., Gemma, S., Catalanotti, B., et al. (2005). Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies. JOURNAL OF MEDICINAL CHEMISTRY, 48(6), 1705-1708 [10.1021/jm049629t].
Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies
Campiani, Giuseppe;Butini, Stefania;Gemma, Sandra;Nacci, Vito;Fiorini, Isabella;
2005-01-01
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 candidate. © 2005 American Chemical Society.
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https://hdl.handle.net/11365/2872
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