TARGETING DELAVIRDINE ATEVIRDINE RESISTANT HIV-1 - IDENTIFICATION OF (ALKYLAMINO)PIPERIDINE-CONTAINING BIS(HETEROARYL)PIPERAZINES AS BROAD-SPECTRUM HIV-1 REVERSE-TRANSCRIPTASE INHIBITORS/

A novel class of bis(heteroaryl)piperazine (BHAP) analogs which posses ses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted sc reening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-B HPSs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were requir ed to inhibit metabolism and modulate solubility in order to obtain co mpounds with the desired biological profile as well as appropriate pha rmaceutical properties. The AAP-BHAPs with the most suitable character istics were compounds 7, 15, and 36.