Biphenyls as potent vitronectin receptor antagonists. Part 3: Squaric acid amides.
Vitronectin receptor (alpha(V)beta(3)) antagonists have been implicated as a possible new treatment of restenosis following balloon angioplasty. In this work we investigate a series of novel arginine mimetic scaffolds leading to new insight of the alpha(V)beta(3)/ligand interaction. Squaric acid amide 10 is a subnanomolar alpha(V)beta(3) antagonist with improved potency on human smooth muscle cell migration.
Urbahns
Klaus
K
Institute of Medicinal Chemistry, Bayer Healthcare AG, Bayer-Schering Pharma, 42096 Wuppertal, Germany. Klaus.Urbahns@astrazeneca.com
Härter
Michael
M
Albers
Markus
M
Schmidt
Delf
D
Stelte-Ludwig
Beatrix
B
Brüggemeier
Ulf
U
Vaupel
Andrea
A
Keldenich
Jörg
J
Lustig
Klemens
K
Tsujishita
Hideki
H
Gerdes
Christoph
C
D001665:Binding Sites / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D003503:Cyclobutanes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D001713:Biphenyl Compounds; D003503:Cyclobutanes; D008024:Ligands; D019030:Receptors, Vitronectin; D013449:Sulfonamides; C527748:squaric acid amide; C020637:squaric acid dibutyl ester