4-(Alkylthio)- and 4-(arylthio)-benzonitrile derivatives as androgen receptor antagonists for the topical suppression of sebum production

The first examples of thioether-substituted benzonitrilesas potential soft-drug androgen receptorantagonists are reported. A number of 4-(alkylthio)- and of 4-(arylthio)- benzonitrile analogswere evaluated in human androgen receptorbinding and cellular functional assays. Analogswith potent in vitro binding and cellular activities were evaluated for topical in vivo efficacy in the Golden Syrian hamsterear model. Analogsfrom both the 4-(alkylthio)- and of 4-(arylthio)- benzonitrileseries showed moderate reduction of wax estersin vivo.