Highly potent and selective alphaVbeta3-receptor antagonists: solid-phase synthesis and SAR of 1-substituted 4-amino-1H-pyrimidin-2-ones.
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.
Zechel
Christian
C
BASF AG, D-67056 Ludwigshafen, Germany. zechel_christian@lilly.com
Backfisch
Gisela
G
Delzer
Jürgen
J
Geneste
Hervé
H
Graef
Claudia
C
Hornberger
Wilfried
W
Kling
Andreas
A
Lange
Udo E W
UE
Lauterbach
Arnulf
A
Seitz
Werner
W
Subkowski
Thomas
T
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
D006146:Guanidines; D007202:Indicators and Reagents; D039302:Integrin alphaVbeta3; D008024:Ligands; D011744:Pyrimidinones