Synthesis and biological evaluation of dihydrofuran-fused perhydrophenanthrenes as a new anti-influenza agent having novel structural characteristic

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 1; pp. 424 - 432
• Main Authors: Matsuya, Yuji, Sasaki, Kazushige, Ochiai, Hiroshi, Nemoto, Hideo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2007
• Subjects: Animals; Anti-influenza agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Cage structure; Cell Line; Cell Proliferation - drug effects; Dogs; Dose-Response Relationship, Drug; Drug Design; Furans - chemistry; Influenza A virus - drug effects; Influenza A virus - growth & development; Influenza B virus - drug effects; Influenza B virus - growth & development; Influenza virus; Microbial Sensitivity Tests; Molecular Structure; mRNA; Perhydrophenanthrenes; Phenanthrenes - chemistry; Stereoisomerism; Structure-Activity Relationship; Virus Replication - drug effects; Perhydrophenanthrenes; mRNA; Anti-influenza agents; Cage structure
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.09.046

Dihydrofuran-fused perhydrophenanthrenes were synthesized by means of
o-quinodimethane chemistry with high generality and stereoselectivity, and found to exhibit potent anti-influenza activity. These compounds exerted an inhibitory effect on various strains of influenza virus growth, including influenza A and B, with a concentration dependent manner, and direct cytotoxicity was low. Several biological experiments suggested that these new drugs affected a virus replication process before mRNA synthesis stage. Novel rigid cage-type of structural characteristic of the compounds has not been found in hitherto anti-influenza drugs, and will provide new basis and motif for exploring promising and unprecedented anti-influenza agents.