Synthesis and SAR of N-substituted dibenzazepinone derivatives as novel potent and selective alpha(V)beta(3) antagonists.
Synthesis and SARs of new integrin alpha(V)beta(3) antagonists based on an N-substituted dibenzazepinone scaffold are described. Variation of spacer and guanidine mimetic led to potent compounds exhibiting an IC(50) towards alpha(V)beta(3) in the nanomolar range, high selectivity versus integrin alpha(IIb)beta(3) and efficacy in functional cellular assays.
Kling
Andreas
A
Knoll GmbH, D-67008 Ludwigshafen, Germany. andreas.kling@abbott.de
Backfisch
Gisela
G
Delzer
Jürgen
J
Geneste
Hervé
H
Graef
Claudia
C
Holzenkamp
Uta
U
Hornberger
Wilfried
W
Lange
Udo E W
UE
Lauterbach
Arnulf
A
Mack
Helmut
H
Seitz
Werner
W
Subkowski
Thomas
T
D003984:Dibenzazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019791:Guanidine / Q000737:chemistry; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D003984:Dibenzazepines; D005343:Fibrinolytic Agents; D007202:Indicators and Reagents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D019791:Guanidine