199177-26-9Relevant academic research and scientific papers
CLPX INHIBITORY COMPOUNDS FOR THE TREATMENT OF MULTI RESISTANT STAPHYLOCOCCUS AUREUS VIRULENCE AND FOR THE TREATMENT OF LEUKEMIA
-
Page/Page column 26, (2018/07/26)
The present invention relates to antibiotic compounds and their use as ClpX inhibitors and in the treatment of bacterial infections, such as infections with multi-resistant Staphylococcus aureas, and in the treatment of leukemia. The present invention fur
BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability
Jennings, Laura E.,Schiedel, Matthias,Hewings, David S.,Picaud, Sarah,Laurin, Corentine M.C.,Bruno, Paul A.,Bluck, Joseph P.,Scorah, Amy R.,See, Larissa,Reynolds, Jessica K.,Moroglu, Mustafa,Mistry, Ishna N.,Hicks, Amy,Guzanov, Pavel,Clayton, James,Evans, Charles N.G.,Stazi, Giulia,Biggin, Philip C.,Mapp, Anna K.,Hammond, Ester M.,Humphreys, Philip G.,Filippakopoulos, Panagis,Conway, Stuart J.
, p. 2937 - 2957 (2018/05/25)
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t? = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04. Molecular dynamics simulations assisted our understanding of the role played by an internal hydrogen bond in altering the affinity of this series of molecules for BRD4(1). OXFBD04 shows improved BRD4(1) affinity (IC50 = 166 nM), optimised physicochemical properties (LE = 0.43; LLE = 5.74; SFI = 5.96), and greater metabolic stability (t? = 388 min).
A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant Staphylococcus aureus
Fetzer, Christian,Korotkov, Vadim S.,Th?nert, Robert,Lee, Kyu Myung,Neuenschwander, Martin,von Kries, Jens Peter,Medina, Eva,Sieber, Stephan A.
supporting information, p. 15746 - 15750 (2017/10/20)
The Staphylococcus aureus ClpXP protease is an important regulator of cell homeostasis and virulence. We utilized a high-throughput screen against the ClpXP complex and identified a specific inhibitor of the ClpX chaperone that disrupts its oligomeric sta
Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole
Yang, Lingyun,Zhang, Jian,Si, Lianghui,Han, Li,Zhang, Bo,Ma, Hui,Xing, Junhao,Zhao, Leilei,Zhou, Jinpei,Zhang, Huibin
, p. 46 - 58 (2016/04/19)
GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clinical studies using TAK-875 (fasiglifam). In the present studies, we discovered a series of anal
AROMATIC COMPOUNDS, COMPOSITIONS AND USES THEREOF
-
Paragraph 0135; 0141; 0148; 0154; 0160; 0166; 0173; 0184, (2015/12/17)
Aromatic compounds that are bromodomain inhibitors are provided. The compounds may be used in a method of treating cancer. Pharmaceutical compositions comprising an aromatic compound as detailed herein are provided, as are kits comprising a compound or a salt thereof and instructions for use, e.g., in a method of treating cancer.
PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS
-
Page/Page column 106, (2014/05/07)
New pyrrolotriazinone derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks).
Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands
Hewings, David S.,Fedorov, Oleg,Filippakopoulos, Panagis,Martin, Sarah,Picaud, Sarah,Tumber, Anthony,Wells, Christopher,Olcina, Monica M.,Freeman, Katherine,Gill, Andrew,Ritchie, Alison J.,Sheppard, David W.,Russell, Angela J.,Hammond, Ester M.,Knapp, Stefan,Brennan, Paul E.,Conway, Stuart J.
supporting information, p. 3217 - 3227 (2013/06/04)
The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodom
The discovery and synthesis of potent zwitterionic inhibitors of renin
Aspiotis, Renee,Chen, Austin,Cauchon, Elizabeth,Dubé, Daniel,Falgueyret, Jean-Pierre,Gagné, Sébastien,Gallant, Michel,Grimm, Erich L.,Houle, Robert,Juteau, Hélne,Lacombe, Patrick,Laliberté, Sébastien,Lévesque, Jean-Franois,MacDonald, Dwight,McKay, Dan,Percival, M. David,Roy, Patrick,Soisson, Stephen M.,Wu, Tom
scheme or table, p. 2430 - 2436 (2011/05/15)
The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within.
3,4 - SUBSTITUTED PIPERIDINE DERIVATIVES AS RENIN INHIBITORS
-
Page/Page column 27, (2010/06/22)
The present invention relates to 3,4-substituted piperidinyl - based renin inhibitor compounds bearing at 4-position oxopyridine or lsoquinolone and having the formula (I): wherein., S is Formula (IIa) or Formula (IIb). The invention further relates to pharmaceutical compositions containing said compounds, as well as their use in treating cardiovascular events and renal insufficiency.
3, 4 - SUBSTITUTED PIPERIDINE DERIVATIVES AS RENIN INHIBITORS
-
Page/Page column 34, (2009/12/27)
The present invention relates to 3,4-substituted piperidinyl - based renin inhibitor compounds bearing at 4-position lsoqumolone and having the Formula (I) : The invention further relates to pharmaceutical compositions containing said compounds, as well a
