Synthesis and activity of N-Benzyl pseudopeptides HIV protease inhibitors

Article abstract of DOI:10.1016/S0968-0896(02)00563-1

A series of N-benzyl pseudopeptides was designed, synthesized and tested as HIV-1 protease inhibitors. The ability of the new compounds containing N-benzyl hydroxyalkylamino acid core structure to inhibit HIV replication in cell culture is comparable to their capacity to inhibit the isolated enzyme, a result compatible with good pharmacokinetic properties of these derivatives. The pseudotripeptide Fmoc-Leu-N(Bzl)Hse-Met-NH-tBu was the best inhibitor of the series (IC₅₀=170 nM) showing promising inhibition of viral replication (ED₅₀=52 nM). All new compounds exhibit high enzymatic resistance and stability against cell cultures and plasma enzymes.