70254-75-0Relevant academic research and scientific papers
Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
, p. 4623 - 4661 (2021/05/07)
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
Cu-Catalyzed C-H Allylation of Benzimidazoles with Allenes
Dong, Yaxi,Breit, Bernhard
, p. 6765 - 6769 (2021/09/11)
CuH-catalyzed intramolecular cyclization and intermolecular allylation of benzimidazoles with allenes have been described. The reaction proceeded smoothly with the catalytic system of Cu(OAc)2/Xantphos and catalytic amount of (MeO)2MeSiH. This protocol features mild reaction conditions and a good tolerance of substrates bearing electron-withdrawing, electron-donating, or electron-neutral groups. A new catalytic mechanism was proposed for this copper hydride catalytic system.
HYDROXYPYRIDOXAZEPINES AS NRF2 ACTIVATORS
-
Page/Page column 88, (2020/08/28)
The present invention relates hydroxypyridoxazepine compounds, methods of making them, pharmaceutical compositions containing them and their use as Nrf2 activators. In particular, the invention relates to compounds of Formula (I), and pharmaceutically acc
NRF2 COMPOUNDS
-
Page/Page column 20; 45, (2018/07/05)
The present invention relates to a compound which is (R)-3-(1,4- dimethyl-1 H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-2-ethyl-2,3- dihydropyrido[2,3-f][l,4]oxazepin-4(5H)-yl)methyl)-4-methylphenyl) propanoic acid (I), or a pharmaceutically acceptable salt
BISARYL AMIDES AS NRF2 REGULATORS
-
Page/Page column 158, (2018/09/11)
The present invention relates to bisaryl amide analogs, pharmaceutical compositions containing them and their use as NRF2 activators. In particular, the invention relates to bisaryl heterocycles of Formula (I).
ANTIBIOTIC COMPOUNDS
-
Page/Page column 120; 121, (2018/03/25)
The present invention relates to antibiotic compounds of formula (I), to compositions containing these compounds and to methods of treating bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Gram-positive and/or Gram-negative bacteria, and in particular in the treatment of infection with, and diseases caused by, Neisseria gonorrhoeae.
A 'one-pot' phase transfer alkylation/hydrolysis of o-nitrotrifluoroacetanilides. A convenient route to N-alkyl o-phenylenediamines
Brown, Samuel A.,Rizzo, Carmelo J.
, p. 4065 - 4080 (2007/10/03)
A variety of o-nitrotrifluoroacetanilides undergo a one-pot alkylation/hydrolysis to give N-alkyl o-nitroanilines in 40-94% yield. Dimethylsulfate, benzyl bromide and 1-bromo-propane were used as the electrophiles.
?***? Interactions of Flavins, 4. Pyridino-isoalloxazinophanes as Model Systems for Active-Site Complexes in Flavoenzymes: Syntheses, X-Ray Structure Analyses and Spectroscopic Properties
Staab, Heinz A.,Zipplies, Matthias F.,Mueller, Thomas,Storch, Matthias,Krieger, Claus
, p. 1667 - 1680 (2007/10/02)
As model systems for active site complexes in flavoenzymes, flavin and nicotinamide analogues were linked together in cyclophane skeletons of specific sterical structures.Elaborating this concept, we prepared metacyclo(10,6)isoalloxazinophane (3),
