RGD mimetics containing a central hydantoin scaffold: alpkha(v)beta3 vs alpha(IIb)beta3 selectivity requirements.
The synthesis of a series of RGD mimetic alpha(v)beta3 antagonists containing a hydantoin scaffold is shown. The results demonstrate some of the structural requirements for the design of selective alpha(v)beta3 antagonists (vs alpha(IIb)beta3) in terms of the Arg-mimetic, the distance between N- and C-terminus and the lipophilic side chain.
Peyman
A
A
Hoechst Marion Roussel Deutschland GmhH, Frankfurt, Germany. anusch.peyman@hmrag.com
Wehner
V
V
Knolle
J
J
Stilz
H U
HU
Breipohl
G
G
Scheunemann
K H
KH
Carniato
D
D
Ruxer
J M
JM
Gourvest
J F
JF
Gadek
T R
TR
Bodary
S
S
D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis*; D010455:Peptides / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors
D006827:Hydantoins; D007093:Imidazoles; D009842:Oligopeptides; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid; C067623:kistrin; D005340:Fibrinogen