Nonsteroidal Inhibitors of Human Type I Steroid 5α-Reductase

In 1993, researchers discovered benzoquinolinones, a new class of compounds that inhibit the human type I 5α-reductase enzyme, which is involved in producing dihydrotestosterone (DHT) and associated with conditions like benign prostatic hyperplasia, acne, hirsutism, and androgenic alopecia. The study tested these compounds' inhibitory effects on type I 5α-reductase in human foreskin fibroblast cells, finding that the most potent compound, LY191704, had an IC50 of 0.008 µM. The potency of these inhibitors was increased by adding fluorine to the aromatic ring and by creating N-methyl analogs. These compounds were found to be weak inhibitors of type II 5α-reductase and the rat enzyme, indicating species-specific activity. This suggests that benzoquinolinones could be a new treatment option for conditions related to DHT overproduction.