Synthesis of a non-nucleoside reverse transcriptase inhibitor in the alkenyldiarylmethane (ADAM) series with optimized potency and therapeutic index

A novel alkenyldiarylmethane (ADAM) analog has been synthesized with enhanced potency as an anti-HIV agent. The new compound (ADAM II) inhibits the cytopathic effect of HIV-1RF in CEM-SS cells with an EC50 of 13 nM, while it shows cytotoxicity with a CC50of 31.6 μM, providing a therapeutic index of 2430. ADAM II is a non-nucleoside reverse transcriptase inhibitor, displaying an IC50 of 0.3 μM with poly(rC) oligo(dG) as the template/primer.