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Updated: May 9, 2026

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold
Scott A Bolton1, James C Sutton, Rushith Anumula
1Bristol-Myers Squibb Research & Development, Hopewell, NJ 08534-5400, USA. scott.bolton@bms.com
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.
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