Coumarins as novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for potential treatment of prostate cancer

Koichiro Harada; Hideki Kubo; Yoshitaka Tomigahara; Kazuhiko Nishioka; Junya Takahashi; Mio Momose; Shinichi Inoue; Atsuyuki Kojima

doi:10.1016/j.bmcl.2009.10.111

Coumarins as novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for potential treatment of prostate cancer

Bioorg Med Chem Lett. 2010 Jan 1;20(1):272-5. doi: 10.1016/j.bmcl.2009.10.111. Epub 2009 Nov 10.

Authors

Koichiro Harada¹, Hideki Kubo, Yoshitaka Tomigahara, Kazuhiko Nishioka, Junya Takahashi, Mio Momose, Shinichi Inoue, Atsuyuki Kojima

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: 19954971
DOI: 10.1016/j.bmcl.2009.10.111

Abstract

The synthesis and SAR studies of 3- and 4-substituted 7-hydroxycoumarins as novel 17beta-HSD3 inhibitors are discussed. The most potent compounds from this series exhibited low nanomolar inhibitory activity with acceptable selectivity versus other 17beta-HSD isoenzymes and nuclear receptors.

MeSH terms

17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
17-Hydroxysteroid Dehydrogenases / metabolism
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Computer Simulation
Humans
Male
Molecular Conformation
Prostatic Neoplasms / drug therapy
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Umbelliferones / chemical synthesis
Umbelliferones / chemistry*
Umbelliferones / pharmacology

Substances

Antineoplastic Agents
Pyridines
Umbelliferones
17-Hydroxysteroid Dehydrogenases
17beta-hydroxysteroid dehydrogenase type 3