Synthesis and antiviral activity of a new series of 4-isothiazolecarbonitriles

A series of 4-isothiazolecarbonitriles was synthesized and screened for in vitro antiviral activity. The effect of various substituents on the phenyl ring, as well as the substitution of the phenyl for other aromatic and hete roaromatic rings, was examined to establish the requirements for optimum ac tivity. The most active member of the series, 3-methylthio-5-phenyl-4-isoth iazolecarbonitrile, exhibited a high level of activity against enteroviruse s polio 1 and ECHO 9. Preliminary studies on its mechanism of action indica ted that this compound had an effect on an early event in the replication o f poliovirus type 1. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.