摘要
Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D<sub>3sub>/D<sub>2sub> compound (<strong class="boldFont">1strong>) led to a series of new piperazine derivatives having affinity to both dopamine D<sub>3sub> and D<sub>2sub> 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, <strong class="boldFont">2mstrong> (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.