Smoothened antagonists for hair inhibition.

Abstract A series of aminomethylpyrazoles were prepared and evaluated using cell-based Smoothenedβ-lactamase reporter assay and Smoothenedbinding assay. Potent Smoothenedantagonists 10k and 10l were found to inhibit hair growth in vivo in the C3H/HeN mouse hair growth model. The more selective compound 10l was tested negative in the 3T3 NRU assay, indicating a low risk for causing photo-irritation and was efficacious using the C3H/HeN mouse hair growth model although it was slightly less efficacious than that of the reference compound eflornithine( 7 ).