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.
Subject(s)
2-Naphthylamine/chemical synthesis , Cytomegalovirus/chemistry , Naphthalenes/chemical synthesis , Protease Inhibitors/chemical synthesis , Serine Endopeptidases/chemistry , Sulfonamides/chemical synthesis , 2-Naphthylamine/analogs & derivatives , 2-Naphthylamine/chemistry , Databases, Factual , Naphthalenes/chemistry , Protease Inhibitors/chemistry , Structure-Activity Relationship , Sulfonamides/chemistryABSTRACT
The knowledge of SAR in a series of biphenyl anionic RSV inhibitors has been broadened by synthesis and testing of analogs with pyrimidine linkers. Generally, pyrimidine compounds were much harder to synthesize, and their anti-RSV activity was lower in comparison with triazine analogs.