Design, synthesis, and discovery of 5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives: a novel series of mixed dopamine D2/D4 receptor antagonist.
5-piperazinyl-1,2,6,7-tetrahydro-5H-azepino[3,2,1-hi]indol-4-one derivatives were designed, synthesized, and identified as a new series of mixed dopamine D(2)/D(4) receptor antagonists. This series featured a rigid tricyclic ring system as an important pharmacophore core structure for high binding affinity. Molecular modeling studies are also described.
Zhao
He
H
Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405, USA. hzhao@nrgn.com
Zhang
Xiaoyan
X
Hodgetts
Kevin
K
Thurkauf
Andrew
A
Hammer
Jack
J
Chandrasekhar
Jayaraman
J
Kieltyka
Andrzej
A
Brodbeck
Robbin
R
Rachwal
Stanislaw
S
Primus
Renee
R
Manly
Charles
C
D065127:Dopamine D2 Receptor Antagonists; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D009010:Monte Carlo Method; D011485:Protein Binding; D011869:Radioligand Assay; D050638:Receptors, Dopamine D4; D013329:Structure-Activity Relationship
C493599:DRD4 protein, human; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D050638:Receptors, Dopamine D4