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

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

doi:10.1016/s0960-894x(02)00751-5

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

Bioorg Med Chem Lett. 2002 Nov 18;12(22):3329-32. doi: 10.1016/s0960-894x(02)00751-5.

Authors

Joseph P Simeone¹, Robert L Bugianesi, Mitree M Ponpipom, Yi Tien Yang, Jane-Ling Lo, Joel B Yudkovitz, Jisong Cui, George R Mount, Rena Ning Ren, Mellissa Creighton, An-Hua Mao, Stella H Vincent, Kang Cheng, Mark T Goulet

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. joe_simeone@merck.com

PMID: 12392744
DOI: 10.1016/s0960-894x(02)00751-5

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.

MeSH terms

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

Substances

Indoles
Pyridines
Receptors, LHRH
pyridine