Synthesis and Biological Evaluation of Cyclic Sulfamide Derivatives as 11β-Hydroxysteroid Dehydrogenase 1 Inhibitors

被引：18

作者：

Kim, Se Hoan ^{[1
,2
]}

Bok, Ju Han ^{[1
]}

Lee, Jae Hong ^{[1
,2
]}

Kim, Il Hyang ^{[1
,2
]}

Kwon, Sung Wook ^{[1
,2
]}

Lee, Gui Bin ^{[1
]}

Kang, Seung Kyu ^{[1
]}

Park, Ji Seon ^{[1
]}

Jung, Won Hoon ^{[1
]}

Kim, Hee Yeon ^{[1
]}

Rhee, Sang Dal ^{[1
]}

Ahn, Sung Hoon ^{[1
]}

Bae, Myung Ae ^{[1
]}

Ha, Deok Chan ^{[2
]}

Kim, Ki Young ^{[1
]}

Ahn, Jin Hee ^{[1
]}

机构：

[1] Korea Res Inst Chem Technol, Bioorgan Sci Div, Taejon 305600, South Korea

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

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2012年 / 3卷 / 02期

关键词：

diabetes; antidiabetic agents; 11 beta-hydroxysteroid dehydrogenase type 1; cyclic sulfamide; adamantyl group; 11-BETA-HSD1; INHIBITORS; METABOLIC SYNDROME; VISCERAL OBESITY; TYPE-1; MICE; HYPERGLYCEMIA;

D O I：

10.1021/ml200226x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11 beta-HSD1. Among this series, 18e showed good in vitro activity toward human 11 beta-HSD1, selectivity against 11 beta-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.

引用

页码：88 / 93

页数：6

共 16 条

[1] A Convergent Process for the Preparation of Adamantane 11-β-HSD-1 Inhibitors [J].

Becker, Calvin L. ;

Engstrom, Kenneth M. ;

Kerdesky, Francis A. ;

Tolle, John C. ;

Wagaw, Seble H. ;

Wang, Weifeng .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2008, 12 (06) :1114-1118

[2] The development and SAR of pyrrolidine carboxamide 11β-HSD1 inhibitors [J].

Cheng, Hengmiao ;

Hoffman, Jacqui ;

Le, Phuong ;

Nair, Sajiv K. ;

Cripps, Stephan ;

Matthews, Jean ;

Smith, Christopher ;

Yang, Michele ;

Kupchinsky, Stan ;

Dress, Klaus ;

Edwards, Martin ;

Cole, Bridget ;

Walters, Evan ;

Loh, Christine ;

Ermolieff, Jacques ;

Fanjul, Andrea ;

Bhat, Ganesh B. ;

Herrera, Jocelyn ;

Pauly, Tom ;

Hosea, Natilie ;

Paderes, Genevieve ;

Rejto, Paul .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (09) :2897-2902

[3] 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors as Promising Therapeutic Drugs for Diabetes: Status and Development [J].

Ge, R. ;

Huang, Y. ;

Liang, G. ;

Li, X. .

CURRENT MEDICINAL CHEMISTRY, 2010, 17 (05) :412-422

[4] 11β-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress [J].

Kotelevtsev, Y ;

Holmes, MC ;

Burchell, A ;

Houston, PM ;

Schmoll, D ;

Jamieson, P ;

Best, R ;

Brown, R ;

Edwards, CRW ;

Seckl, JR ;

Mullins, JJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (26) :14924-14929

[5] 11-BETA-HYDROXYSTEROID DEHYDROGENASE AND THE SHORT-CHAIN ALCOHOL-DEHYDROGENASE (SCAD) SUPERFAMILY [J].

KROZOWSKI, Z .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1992, 84 (1-2) :C25-C31

[6] Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group [J].

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, Duck Chan ;

Cheon, Hyae Gyoung ;

Kim, Ki Young ;

Ahn, Jin Hee .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (01) :435-439

[7] Bicyclo[2.2.2]octyltriazole inhibitors of 11β-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome [J].

Maletic, Milana ;

Leeman, Aaron ;

Szymonifka, Michael ;

Mundt, Steven S. ;

Zokian, Hratch J. ;

Shah, Kashmira ;

Dragovic, Jasminka ;

Lyons, Kathy ;

Thieringer, Rolf ;

Vosatka, Anne H. ;

Balkovec, James ;

Waddell, Sherman T. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (08) :2568-2572

[8] A transgenic model of visceral obesity and the metabolic syndrome [J].

Masuzaki, H ;

Paterson, J ;

Shinyama, H ;

Morton, NM ;

Mullins, JJ ;

Seckl, JR ;

Flier, JS .

SCIENCE, 2001, 294 (5549) :2166-2170

[9] Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11β-hydroxysteroid dehydrogenase type 1-deficient mice [J].

Morton, NM ;

Paterson, JM ;

Masuzaki, H ;

Holmes, MC ;

Staels, B ;

Fievet, C ;

Walker, BR ;

Flier, JS ;

Mullins, JJ ;

Seckl, JR .

DIABETES, 2004, 53 (04) :931-938

[10] Discovery of adamantane ethers as inhibitors of 11β-HSD-1:: Synthesis and biological evaluation [J].

Patel, Jyoti R. ;

Shuai, Qi ;

Dinges, Jurgen ;

Winn, Marty ;

Pliushchev, Marina ;

Fung, Steven ;

Monzon, Katina ;

Chiou, William ;

Wang, Jiahong ;

Pan, Liping ;

Wagaw, Seble ;

Engstrom, Kenneth ;

Kerdesky, Francis A. ;

Longenecker, Kenton ;

Judge, Russell ;

Qin, Wenying ;

Imade, Hovis M. ;

Stolarik, DeAnne ;

Beno, David W. A. ;

Brune, Michael ;

Chovan, Linda E. ;

Sham, Hing L. ;

Jacobson, Peer ;

Link, J. T. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (03) :750-755

← 1 2 →