cas 302839-09-4, 1-(4-FLUOROPHENYL)-2-(2-FLUORO-4-PYRIDYL)ETHANONE

Articles about 302839-09-4Total 11 be found

Optimized 4,5-diarylimidazoles as potent/selective inhibitors of Protein Kinase CK1δ and their structural relation to P38α MAPK
The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effecti
Halekotte, Jakob,Witt, Lydia,Ianes, Chiara,Krüger, Marc,Bührmann, Mike,Rauh, Daniel,Pichlo, Christian,Brunstein, Elena,Luxenburger, Andreas,Baumann, Ulrich,Knippschild, Uwe,Bischof, Joachim,Peifer, Christian,Koch, Pierre,Laufer, Stefan
(2017/04/03)

KINASE MODULATORS FOR THE TREATMENT OF CANCER
A method of treating cancer in which a compound that inhibits the expression, production or release of IL-10 by immune cells is combined with a compound that stimulates the production of IL-12 when given in combination with, or in the presence of TNFa. Sa
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Paragraph 0243; 0244; 0245

(2017/11/16)

Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site
Inhibition of the epidermal growth factor receptor represents one of the most promising strategies in the treatment of lung cancer. Acquired resistance compromises the clinical efficacy of EGFR inhibitors during long-term treatment. The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition. We used a privileged scaffold with proven cellular potency as well as in vivo efficacy and low toxicity. Guided by molecular modeling, we synthesized and studied the structure-activity relationship of 40 compounds against clinically relevant EGFR mutants. We successfully improved the cellular EGFR inhibition down to the low nanomolar range with covalently binding inhibitors against a gefitinib resistant T790M mutant cell line. We identified additional noncovalent interactions, which allowed us to develop metabolically stable inhibitors with high activities against the osimertinib resistant L858R/T790M/C797S mutant.
Günther, Marcel,Lategahn, Jonas,Juchum, Michael,D?ring, Eva,Keul, Marina,Engel, Julian,Tumbrink, Hannah L.,Rauh, Daniel,Laufer, Stefan
p. 5613 - 5637
(2017/07/22)

An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors
An optimized strategy for the synthesis of the potent p38α mitogen-activated protein kinase inhibitors 2-(2-hydroxyethylsulfanyl)-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (3) and 2-(2,3-dihydroxypropylsulfanyl)-4-(4-fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (4) starting from 2-fluoro-4-methylpyridine is reported. In contrast to a previously published synthesis starting from 2-bromo-4-methylpyridine, the overall yield could be increased from 3.6% to 29.4%. Moreover, this strategy avoids the use of palladium as a catalyst and is more diverse and versatile. Using this optimized protocol, both enantiomers of potent inhibitor 3 were synthesized. Biological data demonstrated that the (S)-enantiomer is the two times more potent eutomer.
El-Gokha, Ahmed,Laufer, Stefan A.,Koch, Pierre
supporting information
p. 10699 - 10704
(2015/11/17)

2-SULFANYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
The invention relates to 2-thio-substituted imidazole derivatives of the Formula I, and to methods of use thereof.
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(2009/10/31)

NEW SUBSTITUTED 1,3-THIAZOLE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF HAVING IMMUNOSUPPRESSION AND INFLAMMATION INHIBITORY ACITIVITY, INTERMEDIATE COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, A PROCESS FOR THE PREPARATION THEREOF, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
Disclosed relates to new substituted 1,3-thiazole derivatives or pharmaceutically acceptable salts thereof having immunosuppresion and inflammation inhibitory activity, intermediate compounds or pharmaceutically acceptable salts thereof, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The compound of the present invention having excellent TNF-α inhibitory activity and inflammation inhibitory activity can be effectively used in the prevention and treatment of TNF-α related diseases.
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Page/Page column 124

(2010/11/25)

A concise and optimized four-step approach toward 2-(aryl-)alkylsulfanyl-, 4(5)-aryl-, 5(4)-heteroaryl-substituted imidazoles using alkyl- or arylalkyl thiocyanates
A convenient cyclization method leading to trisubstituted imidazoles in up to 84% yield is reported. Diverse 1-aryl-, 2-heteroaryl-substituted ethanones are converted into the corresponding α-oximino derivatives which are reduced under regioselective cond
Laufer, Stefan A.,Liedtke, Andy J.
p. 7199 - 7203
(2007/10/03)

2-THIO-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE IN PHARMACEUTICS
The invention relates to 2-thio-substituted imidazole derivatives of formula (I), wherein the radicals R1, R2, R3 and m have the meanings as cited in the description. The inventive compounds comprise an immunomodulatory action and/or an action that inhibits the release of cytokines and are thus suited for treating diseases associated with a disorder of the immune system.
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Page/Page column 59

(2008/06/13)

JNK INHIBITOR
The present invention relates to a c-Jun N-terminal kinase inhibitor containing an azole compound (I) substituted by a nitrogen-containing aromatic group having substituent(s)(except a compound represented by the formula: ) or a salt thereof or a prodrug thereof.
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Page/Page column 89-90

(2010/02/07)

Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes
A series of polysubstituted pyridin-4-yl imidazole inhibitors of p38 MAP (mitogen-activated protein) kinase was prepared as small molecular anticytokine agents and drug candidates for the treatment of chronic inflammatory diseases. The contribution of sub
Laufer, Stefan A.,Wagner, Gerd K.,Kotschenreuther, Dunja A.,Albrecht
p. 3230 - 3244
(2007/10/03)

Photochemical preparation of a pyridone containing tetracycle: A Jak protein kinase inhibitor
Jak3 is a protein tyrosine kinase that is associated with the shared γ chain of receptors for cytokines IL2, IL4, IL7, IL9, and IL13. We have discovered that a pyridone-containing tetracycle (6) may be prepared from trisubstituted imidazole (5) in high yi
Thompson, James E.,Cubbon, Rose M.,Cummings, Richard T.,Wicker, Linda S.,Frankshun, Robert,Cunningham, Barry R.,Cameron, Patricia M.,Meinke, Peter T.,Liverton, Nigel,Weng, Youmin,DeMartino, Julie A.
p. 1219 - 1223
(2007/10/03)