Discovery of cariprazine (RGH-188): A novel antipsychotic acting on dopamine D3/D2 receptors

Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D3/D2 compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D3 and D2 receptors. Several members of this group showed excellent pharmacokinetic and pharmacodynamic properties as demonstrated by outstanding activities in different antipsychotic tests. The most promising representative, 2m (cariprazine) had good absorption, excellent brain penetration and advantageous safety profile. Based on its successful clinical development we are looking forward to the NDA filing of cariprazine in 2012.

Cariprazine, a potential atypical antipsychotic agent has been identified during the optimization of novel series of 4-aryl-piperazine derivatives. The recently available top line results from pivotal clinical trials demonstrated the safety and efficacy of cariprazine in bipolar mania and schizophrenia indications.Figure optionsDownload as PowerPoint slide