Remote functionalization of SCH 39166: discovery of potent and selective benzazepine dopamine D1 receptor antagonists.
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.
Sasikumar
T K
TK
Department of Medicinal Chemistry and Metabolic Disorders, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com
Burnett
Duane A
DA
Greenlee
William J
WJ
Smith
Michelle
M
Fawzi
Ahmad
A
Zhang
Hongtao
H
Lachowicz
Jean E
JE
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
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C058081:ecopipam