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

被引：17

作者：

Kwon, Sung Wook ^{[2
]}

Kang, Seung Kyu ^{[1
]}

Lee, Jae Hong ^{[2
]}

Bok, Joo Hwan ^{[1
]}

Kim, Chi Hyun ^{[1
]}

Rhee, Sang Dal ^{[1
]}

Jung, Won Hoon ^{[1
]}

Kim, Hee Youn ^{[1
]}

Bae, Myung Ae ^{[1
]}

Song, Jin Sook ^{[1
]}

Ha, Duck Chan ^{[2
]}

Cheon, Hyae Gyoung ^{[1
]}

Kim, Ki Young ^{[1
]}

Ahn, Jin Hee ^{[1
]}

机构：

[1] Korea Res Inst Chem Technol, Drug Discovery Div, Taejon 305600, South Korea

[2] Korea Univ, Dept Chem, Seoul 136701, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 01期

关键词：

Diabetes; 11beta-HSD1; Thiazolidine; Adamantyl; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; METABOLIC SYNDROME; VISCERAL OBESITY; TYPE-1; MICE; HYPERGLYCEMIA; DRUGS;

D O I：

10.1016/j.bmcl.2010.10.123

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of thiazolidine derivatives with an adamantyl group was synthesized and evaluated for their ability to inhibit 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-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 11 beta-HSD1, selectivity toward 11 beta-HSD2, metabolic stability, pharmacokinetic, and safety profile. Furthermore, this compound significantly inhibited 11 beta-HSD1 activity in rat and monkey models, and showed improved glycemic control in KKAy mice. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：435 / 439

页数：5

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