Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype.
Aminomethyl-substituted biaryls bearing a pyrazole or triazole moiety were synthesized and investigated for dopamine and serotonin receptor binding. The N-arylpyrazoles 3b,f,g and 4 revealed Ki values in the subnanomolar range (0.28-0.70 nM) for the dopamine D4 receptor subtype. Employing both mitogenesis and GTPgammaS assays, ligand efficacy was evaluated indicating partial agonist properties. Interestingly, the tetrahydropyrimidine 4 (FAUC 2020) displayed significant intrinsic selectivity for D2(long) over D2(short).
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
Stefan
S
Löber
Harald
H
Hübner
Peter
P
Gmeiner
D015394:Molecular Structure; D011485:Protein Binding; D050638:Receptors, Dopamine D4 / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D050638:Receptors, Dopamine D4