Discovery of a potent series of non-steroidal non α-trifluoromethyl carbinol glucocorticoid receptor agonists with reduced lipophilicity

被引：5
|
作者：
Diallo, Hawa [1 ]
Angell, Davina C. [1 ]
Barnett, Heather A. [2 ]
Biggadike, Keith [2 ]
Coe, Diane M. [2 ]
Cooper, Tony W. J. [2 ]
Craven, Andy [2 ]
Gray, James R. [1 ]
House, David [2 ]
Jack, Torquil I. [1 ]
Keeling, Steve P. [2 ]
Macdonald, Simon J. F. [2 ]
Mclay, Iain M.
Oliver, Samuel [1 ]
Taylor, Simon J. [1 ]
Uings, Iain J. [1 ]
Wellaway, Natalie [2 ]
机构：
[1] GlaxoSmithKline Med Res Ctr, Epinova Discovery Performance Unit, Immunoinflammat CEDD, Stevenage SG1 2NY, Herts, England
[2] GlaxoSmithKline Med Res Ctr, Resp Ctr Excellence Drug Discovery CEDD, Stevenage SG1 2NY, Herts, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 04期
关键词：
Glucocorticoid; Non-steroidal; Meta channel; Indazole; Sulfonamide; Low lipophilicity; MODULATORS; BINDING;
D O I：
10.1016/j.bmcl.2010.12.121
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel series of indazole non-steroidal glucocorticoid receptor agonist has been discovered. This series features a sulfonamide central core and meta amides which interact with the extended ligand binding domain. This series has produced some of the most potent and least lipophilic agonists of which we are aware such as 20a (NF kappa B pIC(50) 8.3 (100%), c log P 1.9). Certain analogues in this series also display evidence for modulated pharmacology. (c) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1126 / 1133
页数：8
相关论文
共 50 条
  • [1] Discovery of a potent and dissociated non-steroidal glucocorticoid receptor agonist containing an alkyl carbinol pharmacophore
    Razavi, Hossein
    Riether, Doris
    Harcken, Christian
    Bentzien, Joerg
    Dinallo, Roger M.
    Souza, Donald
    Nelson, Richard M.
    Kukulka, Alison
    Fadra-Khan, Tazmeen N.
    Pack, Edward J., Jr.
    Zuvela-Jelaska, Ljiljana
    Pelletier, Josephine
    Panzenbeck, Mark
    Torcellini, Carol A.
    Proudfoot, John R.
    Nabozny, Gerald H.
    Thomson, David S.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (08) : 1934 - 1940
  • [2] Discovery of New non-steroidal selective glucocorticoid receptor agonists
    Potamitis, Constantinos
    Siakouli, Dimitra
    Papavasileiou, Konstantinos D.
    Boulaka, Athina
    Ganou, Vassiliki
    Roussaki, Marina
    Calogeropoulou, Theodora
    Zoumpoulakis, Panagiotis
    Alexis, Michael N.
    Zervou, Maria
    Mitsiou, Dimitra J.
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2019, 186 : 142 - 153
  • [3] Non-steroidal glucocorticoid agonists
    不详
    [J]. EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (04) : 467 - 470
  • [4] Identification and optimization of non-steroidal glucocorticoid receptor agonists
    Thomson, David S.
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2007, 233 : 578 - 578
  • [5] Identification of dissociated non-steroidal glucocorticoid receptor agonists
    Kuzmich, Daniel
    Kirrane, Tom
    Proudfoot, John
    Bekkali, Younes
    Zindell, Renee
    Beck, Laura
    Nelson, Richard
    Shih, Cheng-Kon
    Kukulka, Alison J.
    Paw, Zofia
    Reilly, Patty
    Deleon, Rodney
    Cardozo, Mario
    Nabozny, Gerald
    Thomson, David
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (18) : 5025 - 5031
  • [6] The discovery of potent and selective non-steroidal glucocorticoid receptor modulators, suitable for inhalation
    Edman, Karl
    Ahlgren, Ragnhild
    Bengtsson, Malena
    Bladh, Hakan
    Backstrom, Stefan
    Dahmen, Jan
    Henriksson, Krister
    Hillertz, Per
    Hulikal, Vijakumar
    Jerre, Anders
    Kinchin, Liz
    Kase, Charlotte
    Lepisto, Matti
    Mile, Irene
    Nilsson, Stinabritt
    Smailagic, Amir
    Taylor, John
    Tjornebo, Ann
    Wissler, Lisa
    Hansson, Thomas
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (11) : 2571 - 2577
  • [7] Discovery of indazole ethers as novel, potent, non-steroidal glucocorticoid receptor modulators
    Hemmerling, Martin
    Edman, Karl
    Lepisto, Matti
    Eriksson, Anders
    Ivanova, Svetlana
    Dahmen, Jan
    Rehwinkel, Hartmut
    Berger, Markus
    Hendrickx, Ramon
    Dearman, Matthew
    Jensen, Tina Jellesmark
    Wissler, Lisa
    Hansson, Thomas
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (23) : 5741 - 5748
  • [8] Advances Toward Dissociated Non-Steroidal Glucocorticoid Receptor Agonists
    Regan, John
    Razavi, Hossein
    Thomson, David
    [J]. ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 43, 2008, 43 : 141 - 154
  • [9] Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate
    Berger, Markus
    May, Ekkehard
    Rehwinkel, Hartmut
    Schaecke, Heike
    Neuhaus, Roland
    Rottmann, Antje
    Zollner, Thomas M.
    Jaroch, Stefan
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (16)
  • [10] Discovery and optimisation of a selective non-steroidal glucocorticoid receptor antagonist
    Brown, Angus R.
    Bosies, Michael
    Cameron, Helen
    Clark, John
    Cowley, Angela
    Craighead, Mark
    Elmore, Moira A.
    Firth, Alistair
    Goodwin, Richard
    Goutcher, Susan
    Grant, Emma
    Grassie, Morag
    Grove, Simon J. A.
    Hamilton, Niall M.
    Hampson, Hannah
    Hillier, Alison
    Ho, Koc-Kan
    Kiczun, Michael
    Kingsbury, Celia
    Kultgen, Steven G.
    Littlewood, Peter T. A.
    Lusher, Scott J.
    MacDonald, Susan
    McIntosh, Lorraine
    McIntyre, Theresa
    Mistry, Ashvin
    Morphy, J. Richard
    Nimz, Olaf
    Ohlmeyer, Michael
    Pick, Jack
    Rankovic, Zoran
    Sherborne, Brad
    Smith, Alasdair
    Speake, Michael
    Spinks, Gayle
    Thomson, Fiona
    Watson, Lynn
    Weston, Mark
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (01) : 137 - 140
12345