Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure-activity relationship

Yoshitake Kanbe, Myung Hwa Kim, Masahiro Nishimoto, Yoshihito Ohtake, Nobuaki Kato, Toshiaki Tsunenari, Kenji Taniguchi, Iwao Ohizumi, Shin ichi Kaiho, Kazumi Morikawa, Jae Chon Jo, Hyun Suk Lim, Hak Yeop Kim

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives with sulfoxide containing side chains at the 4-position were designed, synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure antiestrogens with the ability to downregulate ER, and their in vitro and in vivo antiestrogen activities were similar to those of ICI182,780. In addition, the structure-activity relationship indicated that the (3RS,4RS)-configuration between the 3- and 4-position, the methyl group at the 3-position, the 9-methylene chain between the scaffold and the sulfoxide moiety, and the terminal perfluoroalkyl moiety play an important role in increasing estrogen receptor binding and oral antiestrogen activities.

Original languageEnglish (US)
Pages (from-to)4803-4819
Number of pages17
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number14
DOIs
StatePublished - Jul 15 2006
Externally publishedYes

Keywords

  • Chroman
  • Estrogen
  • Pure antiestrogens
  • Thiochroman

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure-activity relationship'. Together they form a unique fingerprint.

  • Cite this

    Kanbe, Y., Kim, M. H., Nishimoto, M., Ohtake, Y., Kato, N., Tsunenari, T., Taniguchi, K., Ohizumi, I., Kaiho, S. I., Morikawa, K., Jo, J. C., Lim, H. S., & Kim, H. Y. (2006). Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure-activity relationship. Bioorganic and Medicinal Chemistry, 14(14), 4803-4819. https://doi.org/10.1016/j.bmc.2006.03.020