Synthesis and 5α-reductase inhibitory activity of 8-substituted benzo[ƒ]quinolinones derived from palladium mediated coupling reactions

Benzoquinolinones have been shown to be potent, selective inhibitors of the Type I 5α-reductase enzyme, which is responsible for the production of dihydrotestosterone from testosterone localized in the scalp. In an effort to identify compounds that demonstrate inhibition of both 5α-reductase isozymes, we have employed 8-bromobenzoquinolinone as an advanced intermediate for participation in a variety of palladium mediated carbon-carbon bond forming reactions. By varying the 8-substituent it is possible to alter the selectivity profile of the series.