280568-20-9Relevant academic research and scientific papers
Discovery of epigenetic regulator i-bet762: Lead optimization to afford a clinical candidate inhibitor of the bet bromodomains
Mirguet, Olivier,Gosmini, Romain,Toum, Jéro?me,Clément, Catherine A.,Barnathan, Mélanie,Brusq, Jean-Marie,Mordaunt, Jacqueline E.,Grimes, Richard M.,Crowe, Miriam,Pineau, Olivier,Ajakane, Myriam,Daugan, Alain,Jeffrey, Phillip,Cutler, Leanne,Haynes, Andrea C.,Smithers, Nicholas N.,Chung, Chun-Wa,Bamborough, Paul,Uings, Iain J.,Lewis, Antonia,Witherington, Jason,Parr, Nigel,Prinjha, Rab K.,Nicodème, Edwige
, p. 7501 - 7515 (2013/11/06)
The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.
Condensed Azepine Derivatives As Bromodomain Inhibitors
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Page/Page column 38, (2012/08/27)
Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
CONDENSED AZEPINE DERIVATIVES AS BROMODOMAIN INHIBITORS
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Page/Page column 73; 74, (2011/06/11)
Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
1,4-Benzodiazepines as inhibitors of respiratory syncytial virus
Carter, Malcolm C.,Alber, Dagmar G.,Baxter, Robert C.,Bithell, Sian K.,Budworth, Jo,Chubb, Ann,Cockerill, G. Stuart,Dowdell, Verity C. L.,Henderson, Elisa A.,Keegan, Sally J.,Kelsey, Richard D.,Lockyer, Michael J.,Stables, Jeremy N.,Wilson, Lara J.,Powell, Kenneth L.
, p. 2311 - 2319 (2007/10/03)
Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 μM. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.
