title: Modification of the pyridine moiety of non-peptidyl indole GnRH receptor antagonists.
abstract: The synthesis of a number of indole GnRH antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. joe_simeone@merck.com
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Simeone
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bugianesi
authors.forename: Mitree M
authors.initials: MM
authors.lastname: Ponpipom
authors.forename: Yi Tien
authors.initials: YT
authors.lastname: Yang
authors.forename: Jane-Ling
authors.initials: JL
authors.lastname: Lo
authors.forename: Joel B
authors.initials: JB
authors.lastname: Yudkovitz
authors.forename: Jisong
authors.initials: J
authors.lastname: Cui
authors.forename: George R
authors.initials: GR
authors.lastname: Mount
authors.forename: Rena Ning
authors.initials: RN
authors.lastname: Ren
authors.forename: Mellissa
authors.initials: M
authors.lastname: Creighton
authors.forename: An-Hua
authors.initials: AH
authors.lastname: Mao
authors.forename: Stella H
authors.initials: SH
authors.lastname: Vincent
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goulet
mesh_terms: D000284:Administration, Oral; D000478:Alkylation; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D006207:Half-Life; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010084:Oxidation-Reduction; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D011725:Pyridines; D011966:Receptors, LHRH; C023666:pyridine