Synthesis of new 3,4,5-trisubstituted isothiazoles as effective inhibitoryagents of enteroviruses

The synthesis and evaluation of 3,4,5-trisubstituted isothiazoles as antivi ral agents led to the discovery of several compounds effective in vitro aga inst enteroviruses polio 1 and ECHO 9. Structure-activity relationship stud ies revealed that a short thioalkyl chain in the 3-position and a methyl es ter group in the 4-position are the structural components that, to a large extent, contribute to the positive biological profile in terms of both sele ctivity and low cytotoxicity. Under one-step growth conditions, methyl 3-me thylthio-5-phenyl-4-isothiazolecarboxilate caused the greatest activity if added within Ih after poliovirus adsorption. These data suggest interferenc e with early events of viral replication. (C) 1999 Elsevier Science Ltd. Al l rights reserved.