200948-88-5Relevant articles and documents
Development of Bifunctional Thiourea Organocatalysts Derived from a Chloramphenicol Base Scaffold and their Use in the Enantioselective Alcoholysis of meso Cyclic Anhydrides
Yan, Lin-Jie,Wang, Hai-Feng,Chen, Wen-Xue,Tao, Yuan,Jin, Kai-Jun,Chen, Fen-Er
, p. 2249 - 2253 (2016/07/19)
The synthesis of new chloramphenicol-base-derived thiourea organocatalysts, (1S,2R)-12 a–f and (1R,2R)-15 a–c, and their use in the enantioselective alcoholysis of meso-anhydrides are described. In particular, hemiesters afforded excellent enantioselectivities if low loadings of (1S,2R)-12 a–f were used. Almost no enantioselectivities were achieved with the use of (1R,2R)-15 a–c. This technique was used to synthesize (R)-(?)-baclofen.
Binding mode and structure-activity relationships around direct inhibitors of the Nrf2-Keap1 complex
Jnoff, Eric,Albrecht, Claudia,Barker, John J.,Barker, Oliver,Beaumont, Edward,Bromidge, Steven,Brookfield, Frederick,Brooks, Mark,Bubert, Christian,Ceska, Tom,Corden, Vincent,Dawson, Graham,Duclos, Stephanie,Fryatt, Tara,Genicot, Christophe,Jigorel, Emilie,Kwong, Jason,Maghames, Rosemary,Mushi, Innocent,Pike, Richard,Sands, Zara A.,Smith, Myron A.,Stimson, Christopher C.,Courade, Jean-Philippe
supporting information, p. 699 - 705 (2014/05/06)
An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl) methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently. To dock or not to dock? Nrf2 has become an attractive neuroprotective target, as the Nrf2 pathway provides a natural cell defense mechanism against damage. Targeting its physiological negative modulator Keap1 with small molecules may allow Nrf2 to play its protective role. To this end, an X-ray structure of Keap1 co-crystallised with compound (S,R,S)-1 a was obtained, elucidating its binding mode, which in turn helped to drive the drug design process.
Macrocyclic design strategies for small, stable parallel β-sheet scaffolds
Freire, Felix,Gellman, Samuel H.
supporting information; experimental part, p. 7970 - 7972 (2009/12/02)
(Figure Presented) Pairs of short peptide strands can be induced to adopt an antiparallel β-sheet secondary structure in aqueous solution via a macrocyclic constraint, as illustrated by many natural and designedpeptides. We show that an analogous strategy is successful for creation of small units of parallel β-sheet secondary structure in aqueous solution. Cyclization in this case requires nonpeptide segments for N-to -N and C-to-C interstrand linkage. Surprisingly, we find that only one of these segments needs to be preorganized.
