N-(1-Benzylpyrrolidin-3-yl)arylbenzamides as potent and selective human dopamine D4 antagonists.
A series of N-(1-benzylpyrrolidin-3-yl)arylbenzamides 8 has been prepared, and their structure-activity relationships studied. Potent ligands selective for human D(4) (hD(4)) over hD(2) and alpha(1) have been identified. One example was determined to be an antagonist in a cAMP assay, with an IC(50) of 1500 nM.
Egle
Ian
I
NPS Pharmaceuticals Inc., 6850 Goreway Dr., Mississauga, Ontario L4V 1V7, Canada. iegle@npsp.com
Barriault
Nancy
N
Bordeleau
Michel
M
Drage
Jillian
J
Dube
Laurence
L
Peragine
Jack
J
Mazzocco
Lucy
L
Arora
Jalaj
J
Jarvie
Keith
K
Tehim
Ashok
A
D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship
D001549:Benzamides; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D050638:Receptors, Dopamine D4