63492-84-2Relevant academic research and scientific papers
The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor
Gosmini, Romain,Nguyen, Van Loc,Toum, Jér?me,Simon, Christophe,Brusq, Jean-Marie G.,Krysa, Gael,Mirguet, Olivier,Riou-Eymard, Alizon M.,Boursier, Eric V.,Trottet, Lionel,Bamborough, Paul,Clark, Hugh,Chung, Chun-Wa,Cutler, Leanne,Demont, Emmanuel H.,Kaur, Rejbinder,Lewis, Antonia J.,Schilling, Mark B.,Soden, Peter E.,Taylor, Simon,Walker, Ann L.,Walker, Matthew D.,Prinjha, Rab K.,Nicodème, Edwige
, p. 8111 - 8131 (2014/12/10)
Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apolipoprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibition of BET bromodomains. X-ray crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.
Tetrahydroquinoline derivatives as CRTH2 antagonists
Liu, Jiwen,Wang, Yingcai,Sun, Ying,Marshall, Derek,Miao, Shichang,Tonn, George,Anders, Penny,Tocker, Joel,Tang, H. Lucy,Medina, Julio
scheme or table, p. 6840 - 6844 (2010/05/19)
A series of tetrahydroquinoline-derived inhibitors of the CRTH2 receptor was discovered by a high throughput screen. Optimization of these compounds for potency and pharmacokinetic properties led to the discovery of potent and orally bioavailable CRTH2 an
CuI-catalyzed coupling reaction of beta-amino acids or esters with aryl halides at temperature lower than that employed in the normal Ullmann reaction. Facile synthesis of SB-214857.
Ma,Xia
, p. 2583 - 2586 (2007/10/03)
[reaction: see text] The CuI-catalyzed coupling reaction of aryl halides with beta-amino acids or beta-amino esters is completed at 100 degrees C in 48 h, which indicates that the structure of the beta-amino acid has an accelerating effect for the Ullmann
Switching Androgen Receptor Antagonists to Agonists by Modifying C-Ring Substituents on Piperidinoquinolinone
Zhi, Lin,Tegley, Christopher M.,Marschke, Keith B.,Jones, Todd K.
, p. 1008 - 1012 (2007/10/03)
New nonsteroidal human androgen receptor (hAR) agonists were developed from an hAR antagonist pharmacophore, 2(1H-piperidinoquinolinone. (+/-)-trans-7,8-diethyl-4-trifluoromethyl-2(1H)-piperidinoquinolinone was synthesized and demonstrated p
STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
-
, (2008/06/13)
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
-
, (2008/06/13)
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
Steroid receptor modulator compounds and methods
-
, (2008/06/13)
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
-
, (2008/06/13)
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
Tricyclic steroid receptor modulator compounds and methods
-
, (2008/06/13)
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
STEROID RECEPTOR MODULATOR COMPOUNDS AND METHODS
-
, (2008/06/13)
Non-steroidal compounds which are high affinity, high selectivity modulators for steroid receptors are disclosed. Also disclosed are pharmaceutical compositions incorporating such compounds, methods for employing the disclosed compounds and compositions for treating patients requiring steroid receptor agonist or antagonist therapy, intermediates useful in the preparation of the compounds and processes for the preparation of the steroid receptor modulator compounds.
