1004294-58-9Relevant articles and documents
N-(PYRIDIN-2-YL)PYRIDINE-SULFONAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
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Page/Page column 69, (2020/08/22)
The invention relates to heterocyclic compounds of the formula (I) in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders.
NEW 6-AMINO-QUINOLINONE COMPOUNDS AND DERIVATIVES AS BCL6 INHIBITORS
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Page/Page column 93, (2018/07/05)
The present invention encompasses compounds of formula (I), wherein the groups R1 to R5, X, Y and W have the meanings given in the claims and specification, their use as inhibitors of BCL6, pharmaceutical compositions which contain compounds of this kind and their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases.
Discovery and Structure-Guided Optimization of Diarylmethanesulfonamide Disrupters of Glucokinase-Glucokinase Regulatory Protein (GK-GKRP) Binding: Strategic Use of a N → S (nN → σ? S-X) Interaction for Conformational Constraint
Pennington, Lewis D.,Bartberger, Michael D.,Croghan, Michael D.,Andrews, Kristin L.,Ashton, Kate S.,Bourbeau, Matthew P.,Chen, Jie,Chmait, Samer,Cupples, Rod,Fotsch, Christopher,Helmering, Joan,Hong, Fang-Tsao,Hungate, Randall W.,Jordan, Steven R.,Kong, Ke,Liu, Longbin,Michelsen, Klaus,Moyer, Carolyn,Nishimura, Nobuko,Norman, Mark H.,Reichelt, Andreas,Siegmund, Aaron C.,Sivits, Glenn,Tadesse, Seifu,Tegley, Christopher M.,Van, Gwyneth,Yang, Kevin C.,Yao, Guomin,Zhang, Jiandong,Lloyd, David J.,Hale, Clarence,St. Jean, David J.
supporting information, p. 9663 - 9679 (2016/01/12)
The HTS-based discovery and structure-guided optimization of a novel series of GKRP-selective GK-GKRP disrupters are revealed. Diarylmethanesulfonamide hit 6 (hGK-hGKRP IC50 = 1.2 μM) was optimized to lead compound 32 (AMG-0696; hGK-hGKRP IC50 = 0.0038 μM). A stabilizing interaction between a nitrogen atom lone pair and an aromatic sulfur system (nN → σ?S-X) in 32 was exploited to conformationally constrain a biaryl linkage and allow contact with key residues in GKRP. Lead compound 32 was shown to induce GK translocation from the nucleus to the cytoplasm in rats (IHC score = 0; 10 mg/kg po, 6 h) and blood glucose reduction in mice (POC = -45%; 100 mg/kg po, 3 h). X-ray analyses of 32 and several precursors bound to GKRP were also obtained. This novel disrupter of GK-GKRP binding enables further exploration of GKRP as a potential therapeutic target for type II diabetes and highlights the value of exploiting unconventional nonbonded interactions in drug design.