Characterization of mono- and diaminopyrimidine derivatives as novel, nonpeptide gonadotropin releasing hormone (GnRH) receptor antagonists.
A novel series of derivatives of mono- and diaminopyrimidines 1 potently displaced binding of a radiolabeled GnRH analogue to human and rat GnRH receptors. Analogues from these series competitively antagonized GnRH-stimulated increases in extracellular acidification in vitro and suppressed GnRH-mediated increases in circulating luteinizing hormone (LH) in castrated rats and testosterone in intact rats. These compounds or their analogues may be useful in treating sex hormone-dependent disease.
Luthin
David R
DR
Pfizer Global Research and Development-La Jolla/Agouron Pharmaceuticals, Inc., 10724 Science Center Drive, San Diego, CA 92121, USA. david.luthin@pfizer.com
Hong
Yufeng
Y
Tompkins
Eileen
E
Anderes
Kenna L
KL
Paderes
Genevieve
G
Kraynov
Eugenia A
EA
Castro
Mary A
MA
Nared-Hood
Karen D
KD
Castillo
Rosemary
R
Gregory
Margaret
M
Vazir
Haresh
H
May
John M
JM
Anderson
Mark B
MB
D000818:Animals; D002369:Castration; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D007986:Luteinizing Hormone / Q000097:blood / Q000187:drug effects; D008297:Male; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000097:blood
D011743:Pyrimidines; D011966:Receptors, LHRH; D013739:Testosterone; D007986:Luteinizing Hormone