Azaindole derivatives with high affinity for the dopamine D4 receptor: synthesis, ligand binding studies and comparison of molecular electrostatic potential maps.
Piperazinylmethyl substituted pyrazolo[1,5-a]pyridines and related heterocycles were synthesized and found to recognize selectively the dopamine D4 receptor. For the most potent derivative 10d a Ki value of 2.0 nM was observed. SAR studies including the comparison of molecular isopotential surfaces were performed.
Löber
S
S
Institut für Pharmazie und Lebensmittelchemie, Universität Erlangen-Nürnberg, Germany.
Hübner
H
H
Gmeiner
P
P
D018492:Dopamine Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D008956:Models, Chemical; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013499:Surface Properties