Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 1: identification and structure-activity relationships.
Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone 7b. Their related synthesis was also reported.
Zhao
He
H
Neurogen Corporation, 35Northeast Industrial Road, Branford, CT 06405, USA. hzhao@nrgn.com
Thurkauf
Andrew
A
He
Xiaoshu
X
Hodgetts
Kevin
K
Zhang
Xiaoyan
X
Rachwal
Stanislaw
S
Kover
Renata X
RX
Hutchison
Alan
A
Peterson
John
J
Kieltyka
Andrzej
A
Brodbeck
Robbin
R
Primus
Renee
R
Wasley
Jan W F
JW
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005998:Glycine / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D050638:Receptors, Dopamine D4; D011994:Recombinant Proteins / Q000187:drug effects; D013329:Structure-Activity Relationship
C471977:2-(-4-(4-chloro-benzyl)-piperazin-1-yl)-1-(2,3-dihydro-indol-1-yl)-ethanone; C471978:2-(-4-(4-chloro-benzyl)-piperazin-1-yl)-1-(2-methy-2,3-dihydro-indol-1-yl)-ethanone; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D007211:Indoles; D010879:Piperazines; D011994:Recombinant Proteins; D050638:Receptors, Dopamine D4; D005998:Glycine; D011224:Prazosin