Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application

The design and synthesis of novel HIV-1 protease inhibitors (PIs), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was directed towards the discovery of new PIs suitable for a long-acting injectable drug application for treating HIV/AIDS. The two most potent HIV-1 PIs 18 and 22, formulated as nanosuspensions, showed interesting compound release profiles over two months when injected intramuscularly in rats.