50610-14-5Relevant academic research and scientific papers
Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction
Norton, David,Bonnette, William G.,Callahan, James F.,Carr, Maria G.,Griffiths-Jones, Charlotte M.,Heightman, Tom D.,Kerns, Jeffrey K.,Nie, Hong,Rich, Sharna J.,Richardson, Caroline,Rumsey, William,Sanchez, Yolanda,Verdonk, Marcel L.,Willems, Henri?tte M. G.,Wixted, William E.,Wolfe, Lawrence,Woolford, Alison J.-A.,Wu, Zining,Davies, Thomas G.
, p. 15949 - 15972 (2021/11/16)
The NRF2-mediated cytoprotective response is central to cellular homoeostasis, and there is increasing interest in developing small-molecule activators of this pathway as therapeutics for diseases involving chronic oxidative stress. The protein KEAP1, which regulates NRF2, is a key point for pharmacological intervention, and we recently described the use of fragment-based drug discovery to develop a tool compound that directly disrupts the protein-protein interaction between NRF2 and KEAP1. We now present the identification of a second, chemically distinct series of KEAP1 inhibitors, which provided an alternative chemotype for lead optimization. Pharmacophoric information from our original fragment screen was used to identify new hit matter through database searching and to evolve this into a new lead with high target affinity and cell-based activity. We highlight how knowledge obtained from fragment-based approaches can be used to focus additional screening campaigns in order to de-risk projects through the rapid identification of novel chemical series.
Synthetic Entry to Polyfunctionalized Molecules through the [3+2]-Cycloaddition of Thiocarbonyl Ylides
Habiger, Christoph,Haut, Franz-Lucas,Korber, Johannes Nepomuk,Müller, Thomas,Magauer, Thomas,Mayer, Peter,Speck, Klaus,Wurst, Klaus
supporting information, (2019/09/06)
Here we present a comprehensive study on the [3+2]-cycloaddition of thiocarbonyl ylides with a wide variety of alkenes and alkynes. The obtained dihydro- and tetrahydrothiophene products serve as exceptionally versatile intermediates providing access to thiophenes, dienes, dendralenes, and vic-quarternary carbon centers. The use of high-pressure conditions enables thermally unstable, sterically encumbered or moderately reactive substrates to undergo the cycloaddition under mild conditions, thereby increasing the yield by up to 58percent. In addition, we showcase its utility by the formal syntheses of the pharmaceuticals NGB 4420 and tenilapine.
Substituted Sulfonamide Compounds
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Page/Page column 45, (2009/10/17)
Substituted sulfonamide compounds corresponding to the formula I: processes for the preparation thereof, pharmaceutical composition containing these compounds and the use of substituted sulfonamide compounds for the preparation of pharmaceutical compositions.
SUBSTITUTED SULFONAMIDE DERIVATIVES
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Page/Page column 63-64, (2009/10/22)
The invention relates to substituted sulfonamide derivatives, processes for the preparation thereof, medicaments containing these compounds and the use of substituted sulfonamide derivatives for the preparation of medicaments.
SUBSTITUTED SULFONAMIDE DERIVATIVES
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Page/Page column 86; 87, (2009/08/16)
The invention relates to substituted sulfonamide derivatives of the general formula (I'); processes for their preparation, medicaments containing these compounds, and the use of substituted sulfonamide derivatives for the preparation of medicaments
SUBSTITUTED SULFONAMIDE COMPOUNDS
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Page/Page column 30, (2009/10/30)
Substituted sulfonamide compounds corresponding to formula I processes for the preparation thereof, pharmaceutical compositions containing these compounds, and the use of such substituted sulfonamide compounds in pharmaceutical compositions for the treatment and/or inhibition of pain and other conditions at least partly mediated by the bradykinin 1 receptor
Substituted Sulfonamide Compounds
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Page/Page column 43, (2009/01/24)
Substituted sulfonamide compounds corresponding to formula I pharmaceutical compositions comprising them, a process for preparing them, and the use of such compounds to treat or inhibit pain and other disorders or disease states.
