Exploration of novel piperazine or piperidine constructed non-covalent peptidyl derivatives as proteasome inhibitors

A series of novel non-covalent piperazine or piperidine-containing dipeptidyl derivatives possessing a neopentyl-asparagine residue, as exemplified by compound 35, were designed and synthesized. Most of the target compounds exhibited potent in vitro, ex vivo and in vivo proteasome inhibitory activities and anti-proliferation activities against two multiple myeloma cell lines. Additionally, the enzymatic stability of target compound was also improved.193