Design and Synthesis of Serine and Aspartic Protease Inhibitors

摘要: Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-l-hydroxyproline mimic. The hydroxycyclopentene template was synthesized in eight steps from commercially available (syn)-tetrahydrophthalic anhydride. Three different amino acids were explored P1-position and P2-position hydroxyl group cyclopentene substituted with 7-methoxy-2-phenyl-quinolin-4-ol. P3/P4-positions then optimized set six derivatives. All evaluated an vitro assay using full-length protease. Several potent identified, most promising exhibiting Ki value 1.1 nM.