Synthesis of highly potent and selective hetaryl ureas as integrin alpha(V)beta3-receptor antagonists.
Solid-phase synthesis and SAR of integrin alpha(V)beta3-receptor antagonists containing a urea moiety as non-basic guanidine mimetic are described. The most potent compounds exhibited IC(50) values towards alpha(V)beta3 in the nanomolar range and high selectivity versus related integrins like alpha(IIb)beta3. For selected examples efficacy in functional cellular assays is demonstrated.
Lange
Udo E W
UE
BASF AG, D-67056, Ludwigshafen, Germany. udo.lange@basf-ag.de
Backfisch
Gisela
G
Delzer
Jürgen
J
Geneste
Hervé
H
Graef
Claudia
C
Hornberger
Wilfried
W
Kling
Andreas
A
Lauterbach
Arnulf
A
Subkowski
Thomas
T
Zechel
Christian
C
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects*; D006224:Cricetinae; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D019030:Receptors, Vitronectin; D014508:Urea