Modification of the pyridine moiety of non-peptidyl indole GnRH receptor antagonists.

Simeone, Joseph P; Bugianesi, Robert L; Ponpipom, Mitree M; Yang, Yi Tien; Lo, Jane-Ling; Yudkovitz, Joel B; Cui, Jisong; Mount, George R; Ren, Rena Ning; Creighton, Mellissa; Mao, An-Hua; Vincent, Stella H; Cheng, Kang; Goulet, Mark T

Simeone, Joseph P; Bugianesi, Robert L; Ponpipom, Mitree M; Yang, Yi Tien; Lo, Jane-Ling; Yudkovitz, Joel B; Cui, Jisong; Mount, George R; Ren, Rena Ning; Creighton, Mellissa; Mao, An-Hua; Vincent, Stella H; Cheng, Kang; Goulet, Mark T.

Affiliation

Simeone JP; Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. joe_simeone@merck.com

Bioorg Med Chem Lett ; 12(22): 3329-32, 2002 Nov 18.

Article in En | MEDLINE | ID: mdl-12392744

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.

Subject(s)

Indoles/chemical synthesis; Indoles/pharmacokinetics; Receptors, LHRH/antagonists & inhibitors; Administration, Oral; Alkylation; Animals; Biological Availability; Dogs; Half-Life; Indoles/pharmacology; Inhibitory Concentration 50; Oxidation-Reduction; Pyridines/chemistry; Rats; Structure-Activity Relationship

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Collection: 01-internacional Database: MEDLINE Main subject: Receptors, LHRH / Indoles Limits: Animals Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2002 Type: Article Affiliation country: United States

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