Design and synthesis of conformationally constrained arginal thrombin inhibitors

Article abstract of DOI:10.1016/S0960-894X(97)00403-4

A series of conformationally constrained arginal thrombin inhibitors was prepared starting from 5,6 or 5,7 bicyclic lactamic structures, that an indirect approach of X-ray structure-based drug design indicated as D-Phe-Pro dipeptide mimetics. The tetrahydrocquinolyl sulfonamido derivative Ig (LR-D/009) displayed the best inhibitory potency (IC₅₀ = 0.018 μm), with good selectivity over plasmin and trypsin.