Solid-phase synthesis of naphthylamidines as factor VIIa/tissue factor inhibitors

Reductive amination followed by acylation of polymer-linked formyl aryl amidines generate combinatorial libraries of aryl amidines 8–13. Potent small molecule naphthylamidine inhibitors 12 (Ki < 100 nM) of FVIIa/TF have been discovered and their activity against other serine proteases in the coagulation cascade is reported.

Graphical abstractReductive amination followed by acylation of polymer-linked formyl aryl amidines generate combinatorial libraries of aryl amidines. Potent small molecule naphthylamidine inhibitors (Ki < 100 nM) of FVIIa/TF have been discovered and their activity against other serine proteases in the coagulation cascade are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide