Synthesis and structure-activity relationships of thieno[2,3-b]pyrroles as antagonists of the GnRH receptor.
A new class of small-molecule GnRH antagonists, the thieno[2,3-b]pyrroles, was designed. Herein, the synthesis and structure-activity relationships are described. Substitution at the C4 position was investigated; during this study, it was observed that introducing piperazines and piperidines improved the physical properties of the compounds while retaining good in vitro potency. This exploration led to the discovery of amidopiperidines with improved pharmacokinetic properties.
Arnould
Jean Claude
JC
AstraZeneca, Centre de Recherches, PI Pompelle, BP 1050, 51689 Reims Cedex 2, France. jean-claude.arnould@astrazeneca.com
Delouvrié
Bénédicte
B
Boutron
Pascal
P
Dossetter
Al G
AG
Foote
Kevin M
KM
Hamon
Annie
A
Hancox
Urs
U
Harris
Craig S
CS
Hutton
Mike
M
Lamorlette
Maryannick
M
Matusiak
Zbigniew
Z
D000818:Animals; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D011758:Pyrroles; D011966:Receptors, LHRH; D013876:Thiophenes