Di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives: synthesis, dopamine receptor binding and ligand efficacy.
Based on the lead molecule FAUC 113, a series of di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives was synthesized and investigated for their dopamine receptor binding profile. The carbonitrile 11a (FAUC 327) showed excellent pharmacological properties combining high D4 affinity (K(i)=1.5 nM) and selectivity with significant intrinsic activity (31%) in low nanomolar concentrations (EC50=1.5 nM).
Löber
Stefan
S
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052, Erlangen, Germany.
Aboul-Fadl
Tarek
T
Hübner
Harald
H
Gmeiner
Peter
P
D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship
C118215:3-(4-(4-chlorophenyl)piperazinylmethyl)pyrazolo(1,5-a)pyridine; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D008024:Ligands; D011720:Pyrazoles; D011725:Pyridines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4