title: Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors.
abstract: Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) 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.
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary. e.csongor@richter.hu
authors.forename: Eva
authors.initials: E
authors.lastname: Agai-Csongor
authors.forename: György
authors.initials: G
authors.lastname: Domány
authors.forename: Katalin
authors.initials: K
authors.lastname: Nógrádi
authors.forename: János
authors.initials: J
authors.lastname: Galambos
authors.forename: István
authors.initials: I
authors.lastname: Vágó
authors.forename: György Miklós
authors.initials: GM
authors.lastname: Keserű
authors.forename: István
authors.initials: I
authors.lastname: Greiner
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.forename: Anikó
authors.initials: A
authors.lastname: Gere
authors.forename: Eva
authors.initials: E
authors.lastname: Schmidt
authors.forename: Béla
authors.initials: B
authors.lastname: Kiss
authors.forename: Mónika
authors.initials: M
authors.lastname: Vastag
authors.forename: Károly
authors.initials: K
authors.lastname: Tihanyi
authors.forename: Katalin
authors.initials: K
authors.lastname: Sághy
authors.forename: Judit
authors.initials: J
authors.lastname: Laszy
authors.forename: István
authors.initials: I
authors.lastname: Gyertyán
authors.forename: Mária
authors.initials: M
authors.lastname: Zájer-Balázs
authors.forename: Larisza
authors.initials: L
authors.lastname: Gémesi
authors.forename: Margit
authors.initials: M
authors.lastname: Kapás
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szombathelyi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D006801:Humans; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050638:Receptors, Dopamine D4 / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; C533287:cariprazine