- Expeditious Lead Optimization of Isoxazole-Containing Influenza A Virus M2-S31N Inhibitors Using the Suzuki-Miyaura Cross-Coupling Reaction
-
The existence of multidrug-resistant influenza viruses, coupled with the continuously antigenic shift and antigenic drift of influenza viruses, necessitates the development of the next-generation of influenza antivirals. As the AM2-S31N mutant persists in more than 95% of current circulating influenza A viruses, targeting the AM2-S31N proton channel appears to be a logical and valid approach to combating drug resistance. Starting from compound 1, an isoxazole compound with potent AM2-S31N channel blockage and antiviral activity, in this study we report an expeditious synthetic strategy that allows us to promptly explore the structure-activity relationships of isoxazole-containing AM2-S31N inhibitors. Propelled by the convenient synthesis, the lead optimization effort yielded a number of potent antivirals with submicromolar efficacy against several human clinical isolates of influenza A viruses, including both oseltamivir-sensitive and -resistant strains.
- Li, Fang,Hu, Yanmei,Wang, Yuanxiang,Ma, Chunlong,Wang, Jun
-
p. 1580 - 1590
(2017/03/08)
-
- Ring-opening reactions of cyclopropanes. Part 8.1 Nitrosation of donor-acceptor cyclopropanes
-
The reaction of 2,2-dialkoxycyclopropane-1-carboxylates 1a-d and monoalkoxycyclopropane 1e with NOCl gives isoxazoline- and/or isoxazole-3-carboxylates by regioselective ring-opening at C1-C2 bond. A mechanistic interpretation suggests the intermediacy of well-stabilised dipolar species.
- Cermola, Flavio,Di Gioia, Lucrezia,Graziano, Maria Liliana,Iesce, Maria Rosaria
-
p. 677 - 681
(2007/10/03)
-