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

doi:10.1016/j.bmcl.2010.10.123

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 journal › Article › peer-review

17 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 language	English
Pages (from-to)	435-439
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2010.10.123
Publication status	Published - 2011 Jan 1

Bibliographical note

Funding Information:
This research was supported by the Center for Biological Modulators of the 21st Century Frontier R&D Program, the Ministry of Education, Science and Technology, and the Ministry of Knowledge Economy, Korea.

Keywords

11beta-HSD1
Adamantyl
Diabetes
Thiazolidine

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2010.10.123

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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

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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.",

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

note = "Funding Information: This research was supported by the Center for Biological Modulators of the 21st Century Frontier R&D Program, the Ministry of Education, Science and Technology, and the Ministry of Knowledge Economy, Korea. ",

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AU - Bok, Joo Hwan

AU - Kim, Chi Hyun

AU - Rhee, Sang Dal

AU - Jung, Won Hoon

AU - Kim, Hee Youn

AU - Bae, Myung Ae

AU - Song, Jin Sook

AU - Ha, Duck Chan

AU - Cheon, Hyae Gyoung

AU - Kim, Ki Young

AU - Ahn, Jin Hee

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N2 - 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.

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KW - 11beta-HSD1

KW - Adamantyl

KW - Diabetes

KW - Thiazolidine

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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