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
收藏
页码：435 / 439
页数：5
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