title: Indoline and piperazine containing derivatives as a novel class of mixed D(2)/D(4) receptor antagonists. Part 2: asymmetric synthesis and biological evaluation.
abstract: A series of chiral benzylpiperazinyl-1-(2,3-dihydro-indol-1-yl)ethanone derivatives were prepared and examined for their affinity at dopamine D(2) and D(4) receptors. Three compounds having D(2)/D(4) affinity ratios approximating that found for the atypical neuroleptic clozapine were further evaluated in behavioral tests of antipsychotic efficacy and motor side effects.
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: Xiaoshu
authors.initials: X
authors.lastname: He
authors.forename: Andrew
authors.initials: A
authors.lastname: Thurkauf
authors.forename: Diane
authors.initials: D
authors.lastname: Hoffman
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: D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003024:Clozapine / Q000378:metabolism / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D065127:Dopamine D2 Receptor Antagonists; D004353:Drug Evaluation, Preclinical; D004409:Dyskinesia, Drug-Induced / Q000523:psychology; D006207:Half-Life; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4; D011994:Recombinant Proteins / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; C493599:DRD4 protein, human; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; D007202:Indicators and Reagents; D007211:Indoles; D010879:Piperazines; D011994:Recombinant Proteins; C471979:benzylpiperazinyl-1-(2,3-dihydro-indol-1-yl)ethanone; D050638:Receptors, Dopamine D4; D000661:Amphetamine; D003024:Clozapine; D006220:Haloperidol