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Design and syntheses of 1,6-naphthalene derivatives as selective HCMV protease inhibitors
Ariamala Gopalsamy1, Kitae Lim, John W Ellingboe
1Chemical and Screening Sciences and Infectious Diseases,Wyeth Research, Pearl River, NY 10965, USA. gopalsa@wyeth.com
Abstract:
Through high throughput screening of various libraries, substituted styryl naphthalene 6 was identified as an HCMV protease inhibitor. Optimization of various regions of the lead molecule using parallel synthesis resulted in 1,6-substituted naphthalenes 19d-i. These compounds displayed good potency and were selective over elastase, trypsin, and chymotrypsin. The optimization approach on lead compound 6 in three different regions of the molecule using parallel solution-phase synthesis and the corresponding SAR are discussed in detail.
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