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, leading to highly potent and selective factor Xa inhibitors, efficacious in various antithrombotic secondary assays.