Novel 5α-Reductase Inhibitors: Synthesis, Structure-Activity Studies, and Pharmacokinetic Profile of Phenoxybenzoylphenyl Acetic Acids
December 2005
in “
Journal of Medicinal Chemistry
”
TLDR A brominated phenoxy compound effectively inhibits a human enzyme and shows potential for clinical use.
The study synthesized and evaluated novel benzoyl benzoic acids and phenylacetic acids as inhibitors of rat and human steroid 5α-reductase isozymes 1 and 2. These compounds were potent and selective inhibitors of the human type 2 enzyme, with IC50 values in the nanomolar range. A phenylacetic acid derivative with bromination in the 4-position of the phenoxy moiety (compound 12) was the strongest inhibitor, comparable to finasteride, with an IC50 of 5 nM. This compound showed good oral absorption, high bioavailability, and a biological half-life of 5.5 hours in rats, indicating its potential for further clinical evaluation.