Synthesis and biological evaluation of naphthyl phenyl ethers (NPEs) as novel nonnucleoside HIV-1 reverse transcriptase inhibitors

A novel series of naphthyl phenyl ether analogues (NPEs) have been synthesized and evaluated for their in vitro activities against HIV in C8166 cells. Most of the compounds exhibited moderate to excellent anti-HIV activities. Among them the most active compound 12o showed excellent activities against wild-type HIV-1 with an EC50 value of 4.60 nM, along with moderate activities against the double mutant strain HIV-1IIIB A17 (K103N+Y181C) and HIV-2 strain ROD with an EC50 value of 0.82 and 4.40 μM, respectively. Preliminary structure-activity relationship (SAR) among the newly synthesized NPEs was also investigated.