Previous work in this laboratory revealed that tetrahydroquinoline sulfones (in particular, NSC 667952) are effective NNRTIs. When administered with popular nucleoside reverse transcriptase inhibitors commonly used to treat HIV patients a synergistic inhibition of HIV-1 was observed. Many of these drugs remain in use today and are highly toxic with unfavorable pharmacokinetics. Therefore, synthesizing NNRTIs which allow for enhanced reverse transcriptase (RT) inhibition with decreased side effects is highly desired.

In this laboratory, rearrangement of the cyclic aryl aminesulfonanilides to diaryl sulfones with heating in the presence of concentrated acid (sulfuric or phosphoric) provided a convenient one-step route to the sulfones. The tetrahydroquinoline and tetrahydrobenzazepine diaryl sulfones showed anti-viral activity, while the trihydroindoline derivatives are awaiting testing.

Microwave synthesis, when compared to conventional heating methods, often results in increased reaction rates, improved yields, cleaner products and less solvent use. Currently, rearrangement conditions are being optimized for the familiar tetrahydroquinoline sulfonanilides. Our primary goal is to demonstrate advantages and allow for comparison of microwave energy versus conventional heating methods to induce rearrangements to diaryl sulfones.

In hopes of further expanding our knowledge of these rearrangements, we will use the microwave parameters established in the tetrahydroquinoline studies as preliminary conditions for rearrangement studies using pyrrole and phenothiazine sulfonanilides. Conventional rearrangements of pyrrole and phenothiazine derivatives are currently underway for comparison with optimized microwave studies. Our secondary goal is to successfully synthesize biologically valuable diaryl sulfones to obtain a new series of potential NNRTIs.