Highly tractable, sub-nanomolar non-steroidal glucocorticoid receptor agonists

被引：8

作者：

Biggadike, Keith ^{[1
]}

Caivano, Matilde ^{[1
]}

Clackers, Margaret ^{[1
]}

Coe, Diane M. ^{[1
]}

Hardy, George W. ^{[1
]}

Humphreys, Davina ^{[1
]}

Jones, Haydn T. ^{[1
]}

House, David ^{[1
]}

Miles-Williams, Annette ^{[1
]}

Skone, Philip A. ^{[1
]}

Uings, Iain ^{[1
]}

Weller, Vicki ^{[1
]}

McLay, Iain M. ^{[1
]}

Macdonald, Simon J. F. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Resp CEDD, Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 16期

关键词：

Glucocorticoid; Agonist; Non-steroidal; Tractable; MODULATORS; DISCOVERY; FUROATE;

D O I：

10.1016/j.bmcl.2009.06.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NF kappa B agonist activity was optimised in an iterative process from pIC(50) 7.5 (for 7), to pIC(50) 10.1 (for 38E1). An explanation for the SAR observed based is presented along with a proposed docking of 38E1 into the active site of the glucocorticoid receptor. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4846 / 4850

页数：5

共 22 条

[1] AKOUVI O, BIOORG MED CHE UNPUB
[2] Dissociated nonsteroidal glucocorticoid receptor modulators; Discovery of the agonist trigger in a tetrahydronaphthalene-benzoxazine series
Barker, Mike
Clackers, Margaret
Copley, Royston
Demaine, Derek A.
Humphreys, Davina
Inglis, Graham G. A.
Johnston, Michael J.
Jones, Haydn T.
Haase, Michael V.
House, David
Loiseau, Richard
Nisbet, Lesley
Pacquet, Francois
Skone, Philip A.
Shanahan, Stephen E.
Tape, Dan
Vinader, Victoria M.
Washington, Melanie
Uings, Iain
Upton, Richard
Mclay, Iain M.
Macdonald, Simon J. F.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (14) : 4216 - 4231
[3] Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists
Barnett, Heather A.
Coe, Diane M.
Cooper, Tony W. J.
Jack, Torquil I.
Jones, Haydn T.
Macdonald, Simon J. F.
McLay, Iain M.
Rayner, Natalie
Sasse, Rosemary Z.
Shipley, Tracy J.
Skone, Phil A.
Somers, Graham I.
Taylor, Simon
Uings, Iain J.
Woolven, James M.
Weingarten, Gordon G.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (01) : 158 - 162
[4] BIGGADIKE K, 2005, Patent No. 2005005452
[5] BIGGADIKE K, 2007, Patent No. 2007054294
[6] Non-steroidal glucocorticoid agonists - The discovery of aryl pyrazoles as A-ring mimetics
Clackers, Margaret
Coe, Diane M.
Demaine, Derek A.
Hardy, George W.
Humphreys, Davina
Inglis, Graham G. A.
Johnston, Michael J.
Jones, Haydn T.
House, David
Loiseau, Richard
Minick, Doug J.
Skone, Philip A.
Uings, Iain
McLay, Iain M.
Macdonald, Simon J. F.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (17) : 4737 - 4745
[7] ELDRED CD, 2006, Patent No. 2006108699
[8] *GLAXOSMITHKLINE, GLAXOSMITHKLINE 2007
[9] SUBSTITUTED PYRAZOLO CORTICOIDS AS TOPICAL ANTIINFLAMMATORY AGENTS
HANNAH, J
KELLY, K
PATCHETT, AA
STEELMAN, SL
MORGAN, ER
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1975, 18 (02) : 168 - 172
[10] Hughes J, 1998, REV CONTEMP PHARMACO, V9, P569

← 1 2 3 →