Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group

Sung Wook Kwon, Seung Kyu Kang, Jae Hong Lee, Joo Hwan Bok, Chi Hyun Kim, Sang Dal Rhee, Won Hoon Jung, Hee Youn Kim, Myung Ae Bae, Jin Sook Song, Duck Chan Ha, Hyae Gyoung Cheon, Ki Young Kim, Jin Hee Ahn

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

A new series of thiazolidine derivatives with an adamantyl group was synthesized and evaluated for their ability to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Our initial compound 5a showed a weak inhibitory activity. Significant improvements in potency were achieved by substituent modification. The potent compound 8g (E) showed good in vitro inhibitory activity toward human 11β-HSD1, selectivity toward 11β-HSD2, metabolic stability, pharmacokinetic, and safety profile. Furthermore, this compound significantly inhibited 11β-HSD1 activity in rat and monkey models, and showed improved glycemic control in KKAy mice.

Original languageEnglish
Pages (from-to)435-439
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

Keywords

  • 11beta-HSD1
  • Adamantyl
  • Diabetes
  • Thiazolidine

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group'. Together they form a unique fingerprint.

  • Cite this

    Kwon, S. W., Kang, S. K., Lee, J. H., Bok, J. H., Kim, C. H., Rhee, S. D., Jung, W. H., Kim, H. Y., Bae, M. A., Song, J. S., Ha, D. C., Cheon, H. G., Kim, K. Y., & Ahn, J. H. (2011). Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group. Bioorganic and Medicinal Chemistry Letters, 21(1), 435-439. https://doi.org/10.1016/j.bmcl.2010.10.123