Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies.

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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

Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies.

J Med Chem. 2005 Mar 24;48(6):1705-8.

PubMed ID

15771414 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Clozapine	Dopamine D3 receptor	Ki (nM)	319	N/A	N/A	Details
Haloperidol	Dopamine D3 receptor	Ki (nM)	18	N/A	N/A	Details
Olanzapine	Dopamine D3 receptor	Ki (nM)	39	N/A	N/A	Details