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

18 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.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

11beta-HSD1
Adamantyl
Diabetes
Thiazolidine

ASJC Scopus subject areas

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

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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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title = "Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group",

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 - Lee, Jae Hong

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.

AB - 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.

KW - 11beta-HSD1

KW - Adamantyl

KW - Diabetes

KW - Thiazolidine

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SN - 0960-894X

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EP - 439

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 1

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

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