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, Deok-Chan Ha, Hyae Gyoung Cheon, Ki Young Kim, Jin Hee Ahn

Research output: Contribution to journalArticle

11 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

Fingerprint

Thiazolidines
11-beta-Hydroxysteroid Dehydrogenases
Derivatives
Pharmacokinetics
Human Activities
Haplorhini
Rats
Safety

Keywords

  • 11beta-HSD1
  • Adamantyl
  • Diabetes
  • Thiazolidine

ASJC Scopus subject areas

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

Cite this

Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group. / Kwon, Sung Wook; Kang, Seung Kyu; Lee, Jae Hong; Bok, Joo Hwan; Kim, Chi Hyun; Rhee, Sang Dal; Jung, Won Hoon; Kim, Hee Youn; Bae, Myung Ae; Song, Jin Sook; Ha, Deok-Chan; Cheon, Hyae Gyoung; Kim, Ki Young; Ahn, Jin Hee.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 1, 01.01.2011, p. 435-439.

Research output: Contribution to journalArticle

Kwon, SW, Kang, SK, Lee, JH, Bok, JH, Kim, CH, Rhee, SD, Jung, WH, Kim, HY, Bae, MA, Song, JS, Ha, D-C, Cheon, HG, Kim, KY & Ahn, JH 2011, 'Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 1, pp. 435-439. https://doi.org/10.1016/j.bmcl.2010.10.123
Kwon, Sung Wook ; Kang, Seung Kyu ; Lee, Jae Hong ; Bok, Joo Hwan ; Kim, Chi Hyun ; Rhee, Sang Dal ; Jung, Won Hoon ; Kim, Hee Youn ; Bae, Myung Ae ; Song, Jin Sook ; Ha, Deok-Chan ; Cheon, Hyae Gyoung ; Kim, Ki Young ; Ahn, Jin Hee. / Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 1. pp. 435-439.
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