Synthesis of polyhydroxylated aromatics having amidation of piperazine nitrogen as HIV-1 integrase inhibitor

A series of polyhydroxylated aromatics having amidation of piperazine nitrogen were prepared and their HIV-1 IN inhibitory activities were evaluated. The galloyl moiety was a core pharmacophore in the inhibitory of HIV integrase. ( E)- N-[3-(4-Cinnamoylpiperazin-1-yl)propyl]-3,4-dihydroxybenzamide and ( E)- N-[3-(4-cinnamoylpiperazin-1-yl)propyl]-3,4,5-trihydroxybenzamide were designed and synthesized as potential HIV-1 integrase inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, however, corresponding 3,4-dihydroxylated aromatic derivatives appear little inhibition of HIV-1 integrase.