1300031-52-0Relevant articles and documents
NOVEL PROCESS
-
, (2015/12/31)
A compound or a pharmaceutically acceptable salt or solvate thereof with a molecular weight in the range 100 to 750 which inhibits the binding of the first and/or second bromodomains of human BRD-2 to 4 to acetylated lysine residues of their physiological partner which is able to: a) form a hydrogen bonding interaction in which the compound accepts a hydrogen bond from the sidechain NH2 group of the asparagine residue found at: or b) accept a water-mediated hydrogen bond in which the compound accepts a hydrogen bond from a water that is itself hydrogen-bonded to the sidechain hydroxyl of the tyrosine residue found at and c) which are also able to form a Van der Waals interaction with a lipophilic binding region of a binding pocket such that one or more heavy atoms of the said compounds lie within a 5A range of any of the heavy atoms of the following bromodomain residues which define the binding pocket: for use in the treatment of chronic autoimmune and inflammatory conditions, acute inflammatory conditions or cancer.
Tetrahydroquinoline Derivatives Useful As Bromodomain Inhibitors
-
, (2014/02/16)
Tetrahydroquinoline derivatives, pharmaceutical compositions containing such compounds and to their use in therapy.
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.
Bromodomain Inhibitors For Treating Autoimmune And Inflammatory Diseases
-
, (2012/08/28)
The use of compounds in the treatment of autoimmune and inflammatory diseases or conditions, pharmaceutical compositions containing such compounds and to methods for identifying compounds for use in the treatment of such diseases or conditions.
TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS
-
, (2012/11/07)
Tetrahydroquinoline (I) derivatives, pharmaceutical compositions containing such compounds and to their use in therapy.
TETRAHYDROQUINOLINE DERIVATIVES USEFUL AS BROMODOMAIN INHIBITORS
-
, (2012/11/07)
Tetrahydroquinoline compounds (I), pharmaceutical compositions containing such compounds and their use in therapy
THETRAHYDROQUINOLINES DERIVATIVES AS BROMODOMAIN INHIBITORS
-
, (2011/06/11)
Tetrahydroquinoline compounds of formula (I) or a salt thereof, pharmaceutical compositions containing such compounds and their use in therapy, in particular in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.
