Identification of oxazolidinediones and thiazolidinediones as potent 17β-hydroxysteroid dehydrogenase type 3 inhibitors

Koichiro Harada; Hideki Kubo; Akio Tanaka; Kazuhiko Nishioka

doi:10.1016/j.bmcl.2011.10.095

Identification of oxazolidinediones and thiazolidinediones as potent 17β-hydroxysteroid dehydrogenase type 3 inhibitors

Bioorg Med Chem Lett. 2012 Jan 1;22(1):504-7. doi: 10.1016/j.bmcl.2011.10.095. Epub 2011 Nov 12.

Authors

Koichiro Harada¹, Hideki Kubo, Akio Tanaka, Kazuhiko Nishioka

Affiliation

¹ 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

PMID: 22137341
DOI: 10.1016/j.bmcl.2011.10.095

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.

MeSH terms

17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
Carbon / chemistry
Cell Nucleus / metabolism
Chemistry, Pharmaceutical / methods*
Drug Design
Enzyme Inhibitors / pharmacology*
Genes, Reporter
HeLa Cells
Humans
Inhibitory Concentration 50
Isoenzymes / chemistry
Male
Models, Chemical
Models, Molecular
Molecular Conformation
Oxazoles / chemical synthesis
Oxazoles / pharmacology*
Prostate / chemistry
Prostatic Neoplasms / drug therapy*
Thiazolidinediones / chemical synthesis
Thiazolidinediones / pharmacology*

Substances

Enzyme Inhibitors
Isoenzymes
Oxazoles
Thiazolidinediones
Carbon
17-Hydroxysteroid Dehydrogenases
17beta-hydroxysteroid dehydrogenase type 3