Isoxazolidine Conjugates of N3-Substituted 6-Bromoquinazolinones—Synthesis Anti-Varizella-Zoster Virus and Anti-Cytomegalovirus Activity

摘要

1,3-Dipolar cycloaddition of N-methyl C-(diethoxyphosphoryl) nitrone to N3-substituted 6-bromo-2-vinyl-3H-quinazolin-4-ones gave (3-diethoxyphosphoryl) isoxazolidines substituted at C5 with quinazolinones modified at N3. All isoxazolidine cycloadducts were screened for antiviral activity against a broad spectrum of DNA and RNA viruses. Several isoxazolidines inhibited the replication of both thymidine kinase wild-type and deficient (TK⁺ and TK⁻) varicella-zoster virus strains at EC50 in the 5.4–13.6 μΜ range, as well as human cytomegalovirus (EC50 = 8.9–12.5 μΜ). Isoxazolidines trans->11b, trans->11c, trans->11e, trans->11f/cis->11f, trans->11g, trans->11h, and trans->11i/cis->11i exhibited moderate cytostatic activity towards the human lymphocyte cell line CEM (IC50 = 9.6–17 μM).