title: Synthesis and structure-activity relationships of thieno[2,3-b]pyrroles as antagonists of the GnRH receptor.
abstract: 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.
authors.affiliation: AstraZeneca, Centre de Recherches, PI Pompelle, BP 1050, 51689 Reims Cedex 2, France. jean-claude.arnould@astrazeneca.com
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Arnould
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Delouvrié
authors.forename: Pascal
authors.initials: P
authors.lastname: Boutron
authors.forename: Al G
authors.initials: AG
authors.lastname: Dossetter
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Foote
authors.forename: Annie
authors.initials: A
authors.lastname: Hamon
authors.forename: Urs
authors.initials: U
authors.lastname: Hancox
authors.forename: Craig S
authors.initials: CS
authors.lastname: Harris
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
authors.forename: Maryannick
authors.initials: M
authors.lastname: Lamorlette
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Matusiak
mesh_terms: 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
chemical_list: D011758:Pyrroles; D011966:Receptors, LHRH; D013876:Thiophenes