Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists.
Vasopressin 1b (V1b) antagonists have been postulated as possible treatments for depression and anxiety. A novel series of potent and selective V1b antagonists has been identified starting from an in-house screen hit. The incorporation of a sulfonamide linker between a tetrahydroisoquinoline core and amino piperidine lead to the identification of a V1b antagonist with similar affinity for human and rat receptors. Further optimization of the right hand portion afforded potent V1b antagonists that possessed moderate to high selectivity over other receptors.
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jack.scott@spcorp.com
Jack D
JD
Scott
Michael W
MW
Miller
Sarah W
SW
Li
Sue-Ing
SI
Lin
Henry A
HA
Vaccaro
Liwu
L
Hong
Deborra E
DE
Mullins
Mario
M
Guzzi
Jay
J
Weinstein
Robert A
RA
Hodgson
Geoffrey B
GB
Varty
Andrew W
AW
Stamford
Tin-Yau
TY
Chan
Brian A
BA
McKittrick
William J
WJ
Greenlee
Tony
T
Priestley
Eric M
EM
Parker
D000818:Animals; D050034:Antidiuretic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D065092:Antidiuretic Hormone Receptor Antagonists; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D050034:Antidiuretic Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D011804:Quinolines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D013449:Sulfonamides; C037219:quinoline