777875-45-3Relevant academic research and scientific papers
Novel 5α-reductase inhibitors: Synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids
Salem, Ola I. A.,Frotscher, Martin,Scherer, Christiane,Neugebauer, Alexander,Biemel, Klaus,Streiber, Martina,Maas, Ruth,Hartmann, Rolf W.
, p. 748 - 759 (2007/10/03)
Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5α-reductase isozymes 1 and 2, The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC50 values in the nanomolar range. The phenylacetic acid derivatives were more potent than the analogous benzoic acids. Bromination in the 4-position of the phenoxy moiety led to the strongest inhibitor in this class (12; IC50 = 5 nM), which was equipotent to finasteride. Since oral absorption is essential for a potential drug, 12 was further examined. In the parallel artificial membrane permeation assay (PAMPA) it turned out to be a good permeator, whereas it was a medium permeator in Caco2 cells. After oral administration (40 mg/kg) to rats a high bioavailability and a biological half-life of 5.5 h were observed, making it a promising candidate for clinical evaluation.
