title: Identification of oxazolidinediones and thiazolidinediones as potent 17β-hydroxysteroid dehydrogenase type 3 inhibitors.
abstract: Novel and potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) were identified based on oxazolidinedione and thiazolidinedione derivatives, starting from a high-throughput screening hit, 5-(3-bromo-4-hydroxybenzyl)-3-(4-methoxyphenyl)-1,3-thiazol-2-one. 5-(3-Bromo-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one exhibited a promising activity profile and demonstrated significant selectivity over the related 17β-HSD isoenzymes and nuclear receptors.
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd, 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka 554-8558, Japan. haradak@sc.sumitomo-chem.co.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Harada
authors.forename: Hideki
authors.initials: H
authors.lastname: Kubo
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishioka
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D002244:Carbon / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000737:chemistry; D008297:Male; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010080:Oxazoles; D045162:Thiazolidinediones; D002244:Carbon; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3