1-(3-Aryloxyaryl)benzimidazole sulfones are liver X receptor agonists

被引：29

作者：

Travins, Jeremy M. ^{[1
]}

Bernotas, Ronald C. ^{[1
]}

Kaufman, David H. ^{[1
]}

Quinet, Elaine ^{[2
]}

Nambi, Ponnal ^{[2
]}

Feingold, Irene ^{[3
]}

Huselton, Christine ^{[3
]}

Wilhelmsson, Anna ^{[4
]}

Goos-Nilsson, Annika ^{[4
]}

Wrobel, Jay ^{[1
]}

机构：

[1] Wyeth Pharmaceut, Chem Sci, Collegeville, PA 19426 USA

[2] Wyeth Pharmaceut, Cardiovasc & Metab Dis, Collegeville, PA 19426 USA

[3] Wyeth Pharmaceut, Drug Safety & Metab, Collegeville, PA 19426 USA

[4] Karo Bio AB, Novum, S-14157 Huddinge, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 02期

关键词：

Benzimidazole; Sulfone; ABCA1; LXR; Liver X receptor; Cholesterol; Lipid; Atherosclerosis; COUPLING REACTION; ARYL HALIDES; LXR-ALPHA; BENZIMIDAZOLES; INFLAMMATION; CHOLESTEROL; METABOLISM; MODULATORS; QUINOLINES; ARYLATION;

D O I：

10.1016/j.bmcl.2009.11.099

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1-(3-aryloxyaryl)benzimidazoles incorporating a sulfone substituent (6) was prepared. High affinity LXR ligands were identified (LXR beta binding IC50 values <10 nM), some with excellent agonist potency and efficacy in a functional assay of LXR activity measuring ABCA1 mRNA increases in human macrophage THP1 cells. The compounds were typically stable in liver microsome preparations and had good oral exposure in mice. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：526 / 530

页数：5

共 39 条

[1] The ABCs of sterol transport
Baldan, Angel
Bojanic, Dragana D.
Edwards, Peter A.
[J]. JOURNAL OF LIPID RESEARCH, 2009, 50 : S80 - S85
[2] Baranowski M, 2008, J PHYSIOL PHARMACOL, V59, P31
[3] An update on non-steroidal liver X receptor agonists and their potential use in the treatment of atherosclerosis
Bennett, D. Jonathan
D Brown, Lindsay
Cooke, Andrew J.
Edwards, Andrew S.
[J]. EXPERT OPINION ON THERAPEUTIC PATENTS, 2006, 16 (12) : 1673 - 1699
[4] Integration of metabolism and inflammation by lipid-activated nuclear receptors
Bensinger, Steven J.
Tontonoz, Peter
[J]. NATURE, 2008, 454 (7203) : 470 - 477
[5] Bernotas R. C., 2009, [No title captured], Patent No. [WO 2009086138, 2009086138, WO 2009/086138]
[6] 4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists
Bernotas, Ronald C.
Singhaus, Robert R.
Kaufman, David H.
Travins, Jeremy M.
Ullrich, John W.
Unwalla, Rayomand
Quinet, Elaine
Evans, Mark
Nambi, Ponnal
Olland, Andrea
Kauppi, Bjorn
Wilhelmsson, Anna
Goos-Nilsson, Annika
Wrobel, Jay
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (01) : 209 - 212
[7] 4-(3-Aryloxyaryl)quinoline alcohols are liver X receptor agonists
Bernotas, Ronald C.
Kaufman, David H.
Singhaus, Robert R.
Ullrich, John
Unwalla, Rayomand
Quinet, Elaine
Nambi, Ponnal
Wilhelmsson, Anna
Goos-Nilsson, Annika
Wrobel, Jay
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (23) : 8086 - 8092
[8] Biarylether amide quinolines as liver X receptor agonists
Bernotas, Ronald C.
Singhaus, Robert R.
Kaufman, David H.
Ullrich, John
Fletcher, Horace, III
Quinet, Elaine
Nambi, Ponnal
Unwalla, Rayomand
Wilhelmsson, Anna
Goos-Nilsson, Annika
Farnegardh, Mathias
Wrobel, Jay
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (04) : 1663 - 1670
[9] An improved procedure for the synthesis of benzimidazoles, using palladium-catalyzed aryl-amination chemistry
Brain, CT
Steer, JT
[J]. JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (17) : 6814 - 6816
[10] An intramolecular palladium-catalysed aryl amination reaction to produce benzimidazoles
Brain, CT
Brunton, SA
[J]. TETRAHEDRON LETTERS, 2002, 43 (10) : 1893 - 1895

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