Design and synthesis of pseudo-symmetric HIV protease inhibitors containing a novel hydroxymethylcarbonyl (HMC)-hydrazide isostere.

Pseudo-symmetric HIV-1 protease inhibitors containing a novel HMC-hydrazide isostere as the transition-state mimic were designed and synthesized. Most of the synthetic compounds with varied structures at the P and P' sites around this core unit showed potent inhibitory activity against HIV-1 protease with nanomolar K(i) values.