Novel factor Xa inhibitors based on a 2-carboxyindole scaffold: SAR of P4 substituents in combination with a neutral P1 ligand.
A series of novel, highly potent 2-carboxyindole-based factor Xa inhibitors is described. Structural requirements for P4 ligands in combination with a neutral biaryl P1 ligand were investigated with the 2-carboxyindole scaffold. A diverse set of P4 substituents was identified, which, in conjunction with a biaryl P1 ligand, gave highly potent factor Xa inhibitors, which were also selective versus other proteases and efficacious in various antithrombotic secondary assays.
Nazaré
Marc
M
Aventis Pharma Deutschland GmbH, D-65926 Frankfurt am Main, Germany. marc.navarre@aventis.com
Essrich
Melanie
M
Will
David W
DW
Matter
Hans
H
Ritter
Kurt
K
Urmann
Matthias
M
Bauer
Armin
A
Schreuder
Herman
H
Czech
Jörg
J
Lorenz
Martin
M
Laux
Volker
V
Wehner
Volkmar
V
D065427:Factor Xa Inhibitors; D007211:Indoles / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
D065427:Factor Xa Inhibitors; D007211:Indoles; D008024:Ligands; D015842:Serine Proteinase Inhibitors