Novel sulfonamides having dual dopamine D2 and D3 receptor affinity show in vivo antipsychotic efficacy with beneficial cognitive and EPS profile.
A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesting representative, compound 2, showed potent antipsychotic behaviour coupled with a beneficial cognitive and EPS profile.
Agai-Csongor
Eva
E
Gedeon Richter Ltd, Budapest, 10. PO Box 27, H-1475, Hungary. e.csongor@richter.hu
Nógrádi
Katalin
K
Galambos
János
J
Vágó
István
I
Bielik
Attila
A
Magdó
Ildikó
I
Ignácz-Szendrei
Györgyi
G
Keseru
György Miklós
GM
Greiner
István
I
Laszlovszky
István
I
Schmidt
Eva
E
Kiss
Béla
B
Sághy
Katalin
K
Laszy
Judit
J
Gyertyán
István
I
Zájer-Balázs
Mária
M
Gémesi
Larisza
L
Domány
György
G
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced; D003071:Cognition / Q000187:drug effects*; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007202:Indicators and Reagents; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013449:Sulfonamides; D001058:Apomorphine