title: Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 1: identification and structure-activity relationships.
abstract: 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.
authors.affiliation: Neurogen Corporation, 35Northeast Industrial Road, Branford, CT 06405, USA. hzhao@nrgn.com
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.forename: Andrew
authors.initials: A
authors.lastname: Thurkauf
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: He
authors.forename: Kevin
authors.initials: K
authors.lastname: Hodgetts
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Rachwal
authors.forename: Renata X
authors.initials: RX
authors.lastname: Kover
authors.forename: Alan
authors.initials: A
authors.lastname: Hutchison
authors.forename: John
authors.initials: J
authors.lastname: Peterson
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kieltyka
authors.forename: Robbin
authors.initials: R
authors.lastname: Brodbeck
authors.forename: Renee
authors.initials: R
authors.lastname: Primus
authors.forename: Jan W F
authors.initials: JW
authors.lastname: Wasley
mesh_terms: 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
chemical_list: 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