title: Highly potent and selective alphaVbeta3-receptor antagonists: solid-phase synthesis and SAR of 1-substituted 4-amino-1H-pyrimidin-2-ones.
abstract: Solid-phase synthesis and SAR of alpha(V)beta(3)-receptor antagonists based on a N(1)-substituted 4-amino-1H-pyrimidin-2-one scaffold are described. The most potent compounds exhibited IC(50) values towards alpha(V)beta(3) in the nano- to subnanomolar range and high selectivity versus related integrins like alpha(IIb)beta(3). For selected examples efficacy in functional cellular assays was demonstrated.
authors.affiliation: BASF AG, D-67056 Ludwigshafen, Germany. zechel_christian@lilly.com
authors.forename: Christian
authors.initials: C
authors.lastname: Zechel
authors.forename: Gisela
authors.initials: G
authors.lastname: Backfisch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Delzer
authors.forename: Hervé
authors.initials: H
authors.lastname: Geneste
authors.forename: Claudia
authors.initials: C
authors.lastname: Graef
authors.forename: Wilfried
authors.initials: W
authors.lastname: Hornberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Kling
authors.forename: Udo E W
authors.initials: UE
authors.lastname: Lange
authors.forename: Arnulf
authors.initials: A
authors.lastname: Lauterbach
authors.forename: Werner
authors.initials: W
authors.lastname: Seitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Subkowski
mesh_terms: D020650:Combinatorial Chemistry Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006146:Guanidines / Q000494:pharmacology; D007202:Indicators and Reagents; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008024:Ligands; D018716:Molecular Mimicry; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006146:Guanidines; D007202:Indicators and Reagents; D039302:Integrin alphaVbeta3; D008024:Ligands; D011744:Pyrimidinones