Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold

Abstract In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIIa inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2 ) wherein potent inhibition of factor VIIa is maintained relative to most other related serine proteases. In an unanticipated result, the m -benzamide P1 (compounds 21a and 21b ) proved to be a viable benzamidine replacement, albeit with a 20–40 fold loss in potency against factor VIIa.