Synthesis, Anti-HIV Activity, and Metabolic Stability of New Alkenyldiarylmethane HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

Non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are part of the combination
therapy currently used to treat HIV infection. Based on analogy with known HIV-1 NNRT
inhibitors, 18 novel alkenyldiarylmethanes (ADAMs) containing 5-chloro-2-methoxyphenyl,
3-cyanophenyl, or 3-fluoro-5-trifluoromethylphenyl groups were synthesized and evaluated as
HIV inhibitors. Their stabilities in rat plasma have also been investigated. Although introducing
5-chloro-2-methoxyphenyl or 3-fluoro-5-trifluoromethylphenyl groups into alkenyldiarylmethanes does not maintain the antiviral potency, the structural modification of alkenyldiarylmethanes with a 3-cyanophenyl substituent can be made without a large decrease in
activity. The oxazolidinonyl group was introduced into the alkenyldiarylmethane framework
and found to confer enhanced metabolic stability in rat plasma.