Basic Quinolinonyl Diketo Acid Derivatives as Inhibitors of HIV Integrase and their Activity against RNase H Function of Reverse Transcriptase

A series of antiviral basic quinolinonyl diketoacid derivatives were developed as inhibitors of HIV-1 IN.Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below100 nM for strand transfer and showed a 2 order of magnitudeselectivity over 3′-processing. These strand transfer selectiveinhibitors also inhibited HIV-1 RNase H with low micromolarpotencies. Molecular modeling studies based on both the HIV-1 IN and RNase H catalytic core domains provided newstructural insights for the future development of thesecompounds as dual HIV-1 IN and RNase H inhibitors.