Polycyclic N-benzamido imides with potent activity against vaccinia virus

Abstract

The synthesis and antiviral activity of a series of novel polycyclic analogues of the orthopoxvirus egress inhibitor tecovirimat (ST-246) is presented. Several of these compounds display submicromolar activity against vaccinia virus, and were more potent than cidofovir (CDV). The more active compounds were about 10-fold more active than CDV, with minimum cytotoxic concentrations above 100 μ. Chemical manipulations of the two carbon-carbon double bonds present in the compounds were carried out to further explore the structure-activity relationships of these new polycyclic imides. Hydrogenation of the two carbon-carbon double bonds decreases antiviral activity, whereas either cyclopropanation or epoxidation of the double bonds fully eliminates the antiviral activity. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.