Investigation of the S3 site of thrombin: Design, synthesis and biological activity of 4-substituted 3-amino-2-pyridones incorporating P1-argininals

A novel scaffold for P4-P2 dipeptide mimics containing a rigid pyridone spacer was designed based on a virtual library strategy. Several selected nonpeptidic 4-aralkyl or 4-alkylpyridones incorporating a P1-argininal sequence were prepared. The modeling studies, synthesis and biological activities of these unique pyridone derivatives are reported herein.