Strange February Mornings: Pauline Fondevila

The study aimed to synthesize new steroidal compounds based on the progesterone skeleton to inhibit the enzyme 5alpha-reductase, which is implicated in androgen-dependent diseases like androgenic alopecia. The research focused on creating derivatives such as 16beta-methyl-pregnadiene-3,20-diones and 16beta-phenyl-pregnadiene-3,17a-dione, which were tested in various biological models. The trienones (compounds 30, 31, and 43-46) consistently demonstrated higher 5alpha-reductase inhibitory activity compared to dienones (compounds 27, 32, 33, and 38-42). The study suggested that the trienones' coplanar structure allowed for faster reaction with the enzyme, leading to greater inhibition through an irreversible Michael type addition.