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

  • Bioorg Med Chem Lett. 2011 Jan 1;21(1):435-9. doi: 10.1016/j.bmcl.2010.10.123.
Sung Wook Kwon  1 ,  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
Affiliations
  • 1. Department of Chemistry, Korea University, Seoul 136-701, Republic of Korea.
PMID: 21093259 DOI: 10.1016/j.bmcl.2010.10.123
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.