267243-86-7Relevant articles and documents
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.
Continuous preparation method of trifluoromethyl butenone derivative
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Paragraph 0049-0050, (2021/06/22)
The invention discloses a continuous preparation method of a trifluoromethyl butenone derivative. The continuous preparation method is characterized in that a raw material 1 as shown in a structure (I) in a reaction formula and trifluoroacetyl halide serving as a raw material 2 react in a microchannel reactor to prepare the trifluoromethyl butenone derivative as shown in a structure (II). The structure (I) and the structure (II) are as described in the specification. In the structure (I) and the structure (II), R is an electron donating group and can be conjugated with olefin double bonds; R1 and R2 are independently selected from hydrogen, C1-C20 alkyl groups, aryl groups, and substituted aryl groups or silyl groups; and X is halogen and is selected from fluorine, chlorine, bromine and iodine. The method has the advantages of good process universality, good atom economy, high yield, few byproducts, high product purity and the like.
1-(4-(ISOXAZOL-5-YL)-1H-PYRAZOL-1-YL)-2-METHYLPROPAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS IL-17 AND IFN-GAMMA INHIBITORS FOR TREATING AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATION
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Page/Page column 26; 103, (2019/04/10)
The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein Ar, Z and Y are as described herein and R1 is a group of the structure (formula (II)), wherein n is 0 or 1; R2 is H, deuterium or methyl; R3 is methyl, trilluoromethyl, ethyl, or taken with R2 together forms a cyclopropyl group, or R3 forms a methylene bridge to the carbon atom marked *, which are suitable for the treatment of autoimmune diseases and chronic inflammation.
IL17 AND IFN-GAMMA INHIBITION FOR THE TREATMENT OF AUTOIMMUNE INFLAMMATION
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Page/Page column 22, (2012/08/08)
The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salt or solvate thereof, as anti-inflammatory and immunomodulatory agents.
IL17 AND IFN-GAMMA INHIBITION FOR THE TREATMENT OF AUTOIMMUNE INFLAMMATION
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Page/Page column 37, (2012/08/08)
The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salt or solvate thereof, as anti-inflammatory and immunomodulatory agents.
Method for the production of 2-fluoroacyl-3-aminoacrylic acid derivatives
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Page/Page column 5, (2010/12/26)
The present invention relates to a process for preparing 2-fluoroacyl-3-aminoacrylic acid derivatives by reacting fluorinated carboxylic acids with dialkylaminoacrylic acid derivatives and acid halides.
METHOD FOR PRODUCING FLUORINE-CONTAINING ACYLACETIC ACID DERIVATIVE, METHOD FOR PRODUCING FLUORINE-CONTAINING PYRAZOLECARBOXYLIC ACID ESTER DERIVATIVE, AND METHOD FOR PRODUCING FLUORINE-CONTAINING PYRAZOLECARBOXYLIC ACID DERIVATIVE
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Page/Page column 21, (2011/01/11)
A halogenating agent is added to a mixture including a base, a fluoroalkylcarboxylic acid derivative and an acrylate derivative to produce a fluoroaclyacetic acid derivative represented by the following Formula (3): wherein Rf represents a fluorine containing alkyl group, R1 and R2 represent a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, an arylalkyl grou p or an acyl group, or together represent an atomic group that forms a 5- or 6-memb ered ring containing a nitrogen atom to which R1 and R2 are bonded; R3 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, or an arylalkyl g roup; and R4 represents an alkyl group, a cycloalkyl group, an aryl group, or an aryl alkyl group.
NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVE HAVING 11 BETA-HYDROXYSTEROID DEHYDROGENASE TYPE I INHIBITORY ACTIVITY
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Page/Page column 83, (2010/04/24)
Disclosed is a compound which is useful as an 11β-hydroxysteroid dehydrogenase type 1 inhibitor. A compound represented by the formula: , its pharmaceutically acceptable salt, or a solvate thereof, wherein Ring A is a group represented by the formula: Ring B is optionally substituted heteroaryl, provided that optionally substituted isoxazole is excluded, or optionally substituted heterocycle, R1 is hydrogen or optionally substituted alkyl, R2 is -OR5, -SR5, halogen, halogenated alkyl or the like, R3 is optionally substituted alkyl or the like, R4 is optionally substituted alkyl or the like, R5 is optionally substituted alkyl or the like, R6 is hydrogen or the like, R7 and R8 are each independently hydrogen or the like, R10 and R11 are each independently hydrogen or the like, R12 is optionally substituted alkyl or the like, m and p are each independently integer of 1 to 3.
Design and synthesis of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors
Kaller, Matthew R.,Zhong, Wenge,Henley, Charles,Magal, Ella,Nguyen, Thomas,Powers, David,Rzasa, Robert M.,Wang, Weiya,Xiong, Xiaoling,Norman, Mark H.
scheme or table, p. 6591 - 6594 (2010/05/18)
Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Usin
Pyrid-2-one derivatives and methods of use
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Page 37, (2010/02/07)
Selected compounds are effective for treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stroke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
