Synthesis and anti-influenza evaluation of orally active bicyclic ether derivatives related to zanamivir.
Masuda T, Shibuya S, Arai M, Yoshida S, Tomozawa T, Ohno A, Yamashita M, Honda T.
We synthesized bicyclic ether sialidase inhibitors such as tetrahydro-furan-2-yl, tetrahydro-pyran-2-yl, and oxepan-2-yl derivatives related to zanamivir. These compounds substituted by diol at the C-3' and C-4' positions resulted in the retention of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. Compound 11a in particular showed comparable efficacy in vivo relative to that of oseltamivir phosphate.