Structure-based design of novel groups for use in the P1 position of thrombin inhibitor scaffolds. Part 1: Weakly basic azoles

Despite their relatively weak basicity, simple azoles, specifically imidazoles and aminothiazoles, can function as potent surrogates for the more basic amines (e.g., alkyl amines, amidines, guanidines, etc.) which are most often employed as the P1 ligand in the design of noncovalent small molecule inhibitors of thrombin.

Graphical abstractImidazoles and aminothiazoles, in spite of their weak basicity, have been optimized to function as potent P1 ligands in both a peptide series and a nonpeptide series of noncovalent small molecule thrombin inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide