Applications of 3-aminolactams: design, synthesis, and biological evaluation of a library of potential dimerisation inhibitors of HIV1-protease

In the context of our studies on the applications of 3-aminolactams as conformationally restricted pseudodipeptides, we report here the synthesis of a library of potential dimerisation inhibitors of HIV1-protease. Two of the pseudopeptides were active on the wild type virus (HIV1) at micromolar levels (EC50). Although the peptides showed lower anti-viral activity than previously reported dimerisation inhibitors, our results demonstrate that the piperidone moiety does not prevent cell penetration, and hence that such derivatization is compatible with potential anti-HIV treatment.