Synthesis, biological activity, and three-dimensional quantitative structure-activity relationship model for a series of benzo[c]quinolizin-3-ones, nonsteroidal inhibitors of human steroid 5alpha-reductase 1.

New 5alpha-reductase 1 (5alphaR-1) inhibitors were designed to complete a consistent set of analogues suitable for a 3D QSAR study. These compounds were synthesized by a modification of the aza-Robinson annulation, further functionalized by Pd-catalyzed cross-coupling processes, and were tested with human 5alphaR-1 expressed in Chinese hamster ovary 1827 cells. It turned out that the potency of the resulting inhibitors was strongly dependent on the type of substitution at the 8 position, with the IC(50) values ranging from 8.