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.
Scott
Jack D
JD
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jack.scott@spcorp.com
Miller
Michael W
MW
Li
Sarah W
SW
Lin
Sue-Ing
SI
Vaccaro
Henry A
HA
Hong
Liwu
L
Mullins
Deborra E
DE
Guzzi
Mario
M
Weinstein
Jay
J
Hodgson
Robert A
RA
Varty
Geoffrey B
GB
Stamford
Andrew W
AW
Chan
Tin-Yau
TY
McKittrick
Brian A
BA
Greenlee
William J
WJ
Priestley
Tony
T
Parker
Eric M
EM
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