Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies.
Basic Information
ID: ALA1144408
Journal: J Med Chem
Title: Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies.
Authors: 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 MA, Stasi MA, Di Serio S, Ghirardi O, Tinti O, Carminati P.
Abstract: Using rational drug design to develop atypical antipsychotic drug candidates, we generated novel and metabolically stable pyrrolobenzazepines with an optimized pK(i) 5-HT(2A)/D(2) 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.
CiteXplore: 15771414
DOI: 10.1021/jm049629t
Patent ID: ┄