Polycyclic N-benzamido imides with potent activity against vaccinia virus
Torres, Eva × Duque, María D Camps, Pelayo Naesens, Lieve Calvet, Teresa Font-Bardia, Mercè Vázquez, Santiago #
Wiley - V C H Verlag GmbH & Co. KGaA
ChemMedChem vol:5 issue:12 pages:2072-2078
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 sub-micromolar 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 μM. 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.