17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) catalyzes the oxidation of the potent estradiol (E2) to the less active estrogen estrone (E1). Inhibitors of this enzyme should maintain the local level of E2 in bone tissue when the E2 concentration in the circulation drops and therefore might be useful for the treatment of osteoporosis. In this work, novel non-steroidal spiro-δ-lactone compounds designed as 17β-HSD2 inhibitors were synthesized and their physicochemical and biological properties were investigated. These new spiro-δ-lactones are not sufficiently stable for further development and show low inhibition of the enzyme.
17β-hydroxysteroid dehydrogenase type 2 inhibitors, Drug design, Osteoporosis, Spiro-δ-lactones, Steroidomimetics, Biological Evaluation, Spiro-lactones, Inhibitors, 17-Hydroxysteroid, Dehydrogenase, SDRs, dihydrotestosterone, 4-androstene-3,17-dione, spirolactone derivatives, aromatase inhibitors
Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D-66123Saarbrucken, Germany.