Probing the subpockets of factor Xa reveals two binding modes for inhibitors based on a 2-carboxyindole scaffold: a study combining structure-activity relationship and …

M Nazaré, DW Will, H Matter, H Schreuder…

Index: Nazare, Marc; Will, David W.; Matter, Hans; Schreuder, Herman; Ritter, Kurt; Urmann, Matthias; Essrich, Melanie; Bauer, Armin; Wagner, Michael; Czech, Joerg; Lorenz, Martin; Laux, Volker; Wehner, Volkmar Journal of Medicinal Chemistry, 2005 , vol. 48, # 14 p. 4511 - 4525

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Citation Number: 68

Abstract

Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets of the factor Xa enzyme. Interactions with the subpockets were probed by systematic substitution of the 2-carboxyindole scaffold, in combination with privileged P1 and P4 substituents. Combining the most favorable ...