title: Characterization of mono- and diaminopyrimidine derivatives as novel, nonpeptide gonadotropin releasing hormone (GnRH) receptor antagonists.
abstract: 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.
authors.affiliation: Pfizer Global Research and Development-La Jolla/Agouron Pharmaceuticals, Inc., 10724 Science Center Drive, San Diego, CA 92121, USA. david.luthin@pfizer.com
authors.forename: David R
authors.initials: DR
authors.lastname: Luthin
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Hong
authors.forename: Eileen
authors.initials: E
authors.lastname: Tompkins
authors.forename: Kenna L
authors.initials: KL
authors.lastname: Anderes
authors.forename: Genevieve
authors.initials: G
authors.lastname: Paderes
authors.forename: Eugenia A
authors.initials: EA
authors.lastname: Kraynov
authors.forename: Mary A
authors.initials: MA
authors.lastname: Castro
authors.forename: Karen D
authors.initials: KD
authors.lastname: Nared-Hood
authors.forename: Rosemary
authors.initials: R
authors.lastname: Castillo
authors.forename: Margaret
authors.initials: M
authors.lastname: Gregory
authors.forename: Haresh
authors.initials: H
authors.lastname: Vazir
authors.forename: John M
authors.initials: JM
authors.lastname: May
authors.forename: Mark B
authors.initials: MB
authors.lastname: Anderson
mesh_terms: 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
chemical_list: D011743:Pyrimidines; D011966:Receptors, LHRH; D013739:Testosterone; D007986:Luteinizing Hormone