title: Discovery of new SCH 39166 analogs as potent and selective dopamine D1 receptor antagonists.
abstract: A series of novel dopamine D(1) antagonists derived from functionalization of the D-ring of SCH 39166 were prepared. A number of these compounds displayed subnanomolar D(1) activity and more than 1000-fold selectivity over D(2). We found C-3 derivatization afforded compounds with superior overall profile in comparison to the C-2 and C-4 derivatization. A number of highly potent D(1) antagonists were discovered which have excellent selectivity over other dopamine receptors and improved PK profile compared to SCH 39166.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Qiang
authors.forename: T K
authors.initials: TK
authors.lastname: Sasikumar
authors.forename: Duane A
authors.initials: DA
authors.lastname: Burnett
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Haiqun
authors.initials: H
authors.lastname: Tang
authors.forename: Yuanzan
authors.initials: Y
authors.lastname: Ye
authors.forename: Robert D
authors.initials: RD
authors.lastname: Mazzola
authors.forename: Zhaoning
authors.initials: Z
authors.lastname: Zhu
authors.forename: Brian A
authors.initials: BA
authors.lastname: McKittrick
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Ahmad
authors.initials: A
authors.lastname: Fawzi
authors.forename: Michelle
authors.initials: M
authors.lastname: Smith
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*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C058081:ecopipam