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
收藏
页码：4846 / 4850
页数：5
相关论文
共 50 条
  • [41] Discovery of a chromene-based series of non-steroidal glucocorticoid receptor selective antagonists.
    Hartandi, K
    Brenneman, J
    Akripoulou-Zanze, I
    Ashworth, K
    Winn, M
    Arendsen, DL
    Patel, J
    Pratt, JK
    Wang, JH
    Fung, S
    Kalmanovich, MA
    Grynfarb, M
    Goos-Nilsson, A
    Lane, B
    Von-Geldern, T
    Kym, P
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 223 : A97 - A98
  • [42] Novel, selective non-steroidal glucocorticoid receptor modulators (SGRM's) for the treatment of obesity.
    Liu, KKC
    Morgan, BP
    Dow, RL
    McCarthy, PA
    Dasilva-Jardine, P
    Wilson, TC
    Dalvie, D
    Stevenson, RW
    Hargrove, DM
    LaFlamme, JA
    Yang, XJ
    Moynihan, MS
    Schneider, SR
    Carroll, RS
    Zeng, Y
    Rushing, MA
    Brackett, N
    Wang, SW
    Gallaspy, ML
    Li, JS
    Spitzer, JD
    Trilles, RV
    Woodworth, GF
    Martin, KA
    Nardone, NA
    Lee, ES
    Harper, KW
    Soliman, VF
    Vage, C
    Rockwell, MH
    Swick, AG
    Bordner, J
    [J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 222 : U667 - U667
  • [43] Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine
    Agarwal, Rajiv
    Kolkhof, Peter
    Bakris, George
    Bauersachs, Johann
    Haller, Hermann
    Wada, Takashi
    Zannad, Faiez
    [J]. EUROPEAN HEART JOURNAL, 2021, 42 (02) : 152 - 161
  • [44] 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
  • [45] Therapeutic and Adverse Effects of a Non-Steroidal Glucocorticoid Receptor Ligand in a Mouse Model of Multiple Sclerosis
    Wuest, Simone
    Tischner, Denise
    John, Michael
    Tuckermann, Jan P.
    Menzfeld, Christiane
    Hanisch, Uwe-Karsten
    van den Brandt, Jens
    Luehder, Fred
    Reichardt, Holger M.
    [J]. PLOS ONE, 2009, 4 (12):
  • [46] Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors
    Schade, Markus
    Merla, Beatrix
    Lesch, Bernhard
    Wagener, Markus
    Timmermanns, Simone
    Pletinckx, Katrien
    Hertrampf, Torsten
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (20) : 11801 - 11808
  • [47] The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist
    Madauss, Kevin P.
    Bledsoe, Randy K.
    Mclay, Iain
    Stewart, Eugene L.
    Uings, Iain J.
    Weingarten, Gordon
    Williams, Shawn P.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (23) : 6097 - 6099
  • [48] Non-steroidal progesterone receptor specific ligands
    Allan, GF
    Sui, Z
    [J]. MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2005, 5 (08) : 701 - 708
  • [49] FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice
    Dan-yang Zhu
    Jian Lu
    Rui Xu
    Juan-zhen Yang
    Xiang-rui Meng
    Xing-nan Ou-Yang
    Qiu-ying Yan
    Rui-fang Nie
    Tong Zhao
    Yi-di Chen
    Yin Lu
    Yi-nan Zhang
    Wen-jun Li
    Xu Shen
    [J]. Acta Pharmacologica Sinica, 2022, 43 : 2495 - 2510
  • [50] Classic glucocorticoids versus non-steroidal glucocorticoid receptor modulators: Survival of the fittest regulator of the immune system?
    De Bosscher, Karolien
    Beck, Ilse M.
    Haegeman, Guy
    [J]. BRAIN BEHAVIOR AND IMMUNITY, 2010, 24 (07) : 1035 - 1042
12345