Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens

Yoshitake Kanbe, Myung Hwa Kim, Masahiro Nishimoto, Yoshihito Ohtake, Toshiaki Tsunenari, Kenji Taniguchi, Iwao Ohizumi, Shin ichi Kaiho, Yoshiaki Nabuchi, Setsu Kawata, Kazumi Morikawa, Jae Chon Jo, Hee An Kwon, Hyun Suk Lim, Hak Yeop Kim

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

In order to search for alternatives to the sulfoxide moiety in the long side chain of pure antiestrogens, several molecules that may interact with water in a fashion similar to ICI164,384 were designed and it was found that compounds with the carboxy, the sulfamide, or the sulfonamide instead of the sulfoxide moiety also functioned as pure antiestrogens. Interestingly, the compound possessing the carboxy moiety showed superior antiestrogen activity compared to ICI182,780 when dosed orally. Results of the pharmacokinetic evaluation indicated that the potent antiestrogen activity at oral dosing attributed to both the improved absorption from the intestinal wall and the metabolic stability of the compound in liver.

Original languageEnglish (US)
Pages (from-to)4090-4094
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number15
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Keywords

  • Chroman
  • Estrogen receptor
  • Pure antiestrogen
  • Thiochroman

ASJC Scopus subject areas

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

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  • Cite this

    Kanbe, Y., Kim, M. H., Nishimoto, M., Ohtake, Y., Tsunenari, T., Taniguchi, K., Ohizumi, I., Kaiho, S. I., Nabuchi, Y., Kawata, S., Morikawa, K., Jo, J. C., Kwon, H. A., Lim, H. S., & Kim, H. Y. (2006). Discovery of thiochroman derivatives bearing a carboxy-containing side chain as orally active pure antiestrogens. Bioorganic and Medicinal Chemistry Letters, 16(15), 4090-4094. https://doi.org/10.1016/j.bmcl.2006.04.090