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

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• 作者：É ; va Á ; gai-Csongor ; ^{e.csongor@richter.hu} ; Gyö ; rgy Domá ; ny ; Katalin Nó ; grá ; di ; Já ; nos Galambos ; Istvá ; n Vá ; gó ; Gyö ; rgy Mikló ; s Keser疟 ; Istvá ; n Greiner ; Istvá ; n Laszlovszky ; Anikó ; Gere ; É ; va Schmidt ; Bé ; la Kiss ; Mó ; nika Vastag ; Ká ; roly Tihanyi ; Katalin Sá ; ghy ; Judit Laszy ; Istvá ; n Gyertyá ; n ; Má ; ria Zá ; jer-Balá ; zs ; Larisza Gé ; mesi ; Margit Kapá ; s ; Zsolt Szombathelyi
• 关键词：KPWSJANDNDDRMB-QAQDUYKDSA-N
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 May, 2012
• 卷：22
• 期：10
• 页码：3437-3440
• 文件大小：262 K

摘要

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.