ORGN 634

HIV-1 Protease continues to be an important target for the development of new AIDS therapies.  A novel HIV-1 protease inhibitor (1) has been designed and synthesized, employing a pseudopeptide motif previously developed in our laboratories.  This motif, termed a ?ureidopeptide,? replaces the scissile amide bond in a known peptide substrate of HIV-1 protease with a urea linkage.  Such a modification to the peptide backbone has previously been shown to inhibit proteolytic cleavage with minimal structural modification.  Inhibitor 1 was made by a convergent synthesis involving an oxidative Hoffmann rearrangement to form the central urea.  The synthesis of 1 and its inhibition of HIV-1 protease will be presented.