Identification of substituted 6-amino-4-phenyltetrahydroquinoline derivatives: potent antagonists for the follicle-stimulating hormone receptor.
Substituted 6-amino-4-phenyl-tetrahydroquinoline derivatives are described that are antagonists for the G(s)-protein-coupled human follicle-stimulating hormone (FSH) receptor. These compounds show high antagonistic efficacy in vitro using a CHO cell line expressing the human FSH receptor. Antagonist 10 also showed a submicromolar IC(50) in a more physiologically relevant rat granulosa cell assay and was found to significantly inhibit follicle growth and ovulation in an ex vivo mouse model. This compound class may open the way toward a novel, nonsteroidal approach for contraception.
van Straten
Nicole C R
NC
Lead Discovery Unit, Research and Development, N.V. Organon, P.O. Box 20, 5340 BH Oss, The Netherlands. nicole.vanstraten@organon.com
van Berkel
Twan H J
TH
Demont
Dennis R
DR
Karstens
Willem-Jan F
WJ
Merkx
Remco
R
Oosterom
Julia
J
Schulz
Jürgen
J
van Someren
Richard G
RG
Timmers
Cornelis M
CM
van Zandvoort
Peter M
PM
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008970:Molecular Weight; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011962:Receptors, FSH / Q000819:agonists / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011804:Quinolines; D011962:Receptors, FSH