Title: Introduction of an electron withdrawing group on the hydroxyphenylnaphthol scaffold improves the potency of 17##-hydroxysteroid dehydrogenase type 2 (17##-HSD2) inhibitors.

Abstract: Estrogen deficiency in postmenopausal women or elderly men is often associated with the skeletal disease osteoporosis. The supplementation of estradiol (E2) in osteoporotic patients is known to prevent bone fracture but cannot be administered because of adverse effect. As 17##-hydroxysteroid dehydrogenase type 2 (17##-HSD2) oxidizes E2 to its inactive form estrone (E1) and has been found in osteoblastic cells, it is an attractive target for the treatment of osteoporosis. Twenty-one novel, naphthalene-derived compounds have been synthesized and evaluated for their 17##-HSD2 inhibition and their selectivity toward 17##-HSD1 and the estrogen receptors (ERs) ## and ##. Compound 19 turned out to be the most potent and selective inhibitor of 17##-HSD2 in cell-free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17##-HSD2. It also showed marked inhibition of the E1-formation by the rat and mouse orthologous enzymes and strong inhibition of monkey 17##-HSD2. It is thus an appropriate candidate to be further evaluated in a disease-oriented model.
(PMID: 21972996)

ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 19

ChEMBL target type: Target is a single protein chain