Design, synthesis and biological of new potential reverse transcriptase inhibitors containing acyclic phosphonate

AIDS is a disease caused by the HIV. Data from the UNAIDS indicate that in 2017 there were approximately 1.8 million new infections, with 36.9 million people living with HIV worldwide.1 For its treatment a combination of antiretroviral drugs is indicated, however, due to viral resistance, it is necessary the search for new therapeutic options. Our research group has synthesized efavirenz analogues that have shown excellent biological activity.2-3 These molecules were designed via molecular hybridization tool between the efavirenz analogues synthesized by our group that showed TR inhibition, and an acyclic phosphonate chain, similar to the structure of tenofovir. Eight products were synthesized, with a high degree of purity The inhibitory activity of the final compounds was evaluated on a TRHXB2 RNA-dependent DNA polymerase (RDDP), using recombinant purified HIV-1 enzyme. The most promising compounds were 4a and 4d, exhibiting IC50 of 16.91 μM and 21.95 μM, respectively