Synthesis Of Novel HIV-1 Virus Assembly Inhibitors

The HIV infection has possessed a serious threat to human health. Up to date, more than30million people have died of this disease worldwide. Tremendous pharmaceutical research and financial resources have been invested in development of HIV vaccine and anti-HIV drugs. Therapies with numerous marketed drugs are available for various mechanisms during HIV virus infectious cycle, however, the rate of transmitted drug resistance is increasing rapidly. Therefore, targeting a novel mechanism such as HIV virus assembly is in urgent need and should offer an attractive approach to combat HIV variants in the clinic.In the present thesis, poly-substituted indole intermediates have been synthesized in multi-step reactions from4-chloroindole by acylation and reduction. Starting from the readily attainable phenylalanine, the key intermediate C has been synthesized by condensation, de-protection and acylation reactions. Furthermore, the coupling reaction between intermediates A and C afforded two corresponding target compounds, which were evaluated in cell based biological assay and exhibited strong inhibitory effects on the assembly of the HIV-1virus.