Discovery of cariprazine (RGH-188): A novel antipsychotic acting on dopamine Db>3b>/Db>2b> receptors

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• 作者：É ; va Á ; gai-Csongor ; ^{e.csongor@richter.hu} ; Gy&ouml ; rgy Domá ; ny ; Katalin Nó ; grá ; di ; Já ; nos Galambos ; Istvá ; n Vá ; gó ; Gy&ouml ; 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 Db>3b>/Db>2b> compound (boldFont">1) led to a series of new piperazine derivatives having affinity to both dopamine Db>3b> and Db>2b> 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, boldFont">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.