title: Remote functionalization of SCH 39166: discovery of potent and selective benzazepine dopamine D1 receptor antagonists.
abstract: A series of novel benzazepine derived dopamine D(1) antagonists have been discovered. These compounds are highly potent at D(1) and showed excellent selectivity over D(2) and D(4) receptors. SAR studies revealed that a variety of functional groups are tolerated on the D-ring of known tetracyclic benzazepine analog 2, SCH 39166, leading to compounds with nanomolar potency at D(1) and good selectivity over D(2)-like receptors.
authors.affiliation: Department of Medicinal Chemistry and Metabolic Disorders, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com
authors.forename: T K
authors.initials: TK
authors.lastname: Sasikumar
authors.forename: Duane A
authors.initials: DA
authors.lastname: Burnett
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Michelle
authors.initials: M
authors.lastname: Smith
authors.forename: Ahmad
authors.initials: A
authors.lastname: Fawzi
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jean E
authors.initials: JE
authors.lastname: Lachowicz
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000737:chemistry* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C058081:ecopipam