Design and Syntheses of 1,6-Naphthalene Derivatives as Selective HCMV Protease Inhibitors

Through high throughput screening of various libraries, substituted styryl naphthalene <BO>6</BO> was identified as an HCMV protease inhibitor. Optimization of various regions of the lead molecule using parallel synthesis resulted in 1,6-substituted naphthalenes <BO>19d</BO>−<BO>i</BO>. These compounds displayed good potency and were selective over elastase, trypsin, and chymotrypsin. The optimization approach on lead compound <BO>6</BO> in three different regions of the molecule using parallel solution-phase synthesis and the corresponding SAR are discussed in detail.