- Discovery of BAY-985, a Highly Selective TBK1/IKK? Inhibitor
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The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKK? are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKK? inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.
- Lefranc, Julien,Schulze, Volker Klaus,Hillig, Roman Christian,Briem, Hans,Prinz, Florian,Mengel, Anne,Heinrich, Tobias,Balint, Jozsef,Rengachari, Srinivasan,Irlbacher, Horst,St?ckigt, Detlef,B?mer, Ulf,Bader, Benjamin,Gradl, Stefan Nikolaus,Nising, Carl Friedrich,Von Nussbaum, Franz,Mumberg, Dominik,Panne, Daniel,Wengner, Antje Margret
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p. 601 - 612
(2020/02/04)
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- Mycobacterium tuberculosis Decaprenylphosphoryl-β- d -ribose Oxidase Inhibitors: Expeditious Reconstruction of Suboptimal Hits into a Series with Potent in Vivo Activity
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Decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) is an essential enzyme in Mycobacterium tuberculosis and has recently been studied as a potential drug target, with inhibitors progressing to clinical studies. Here we describe the identification of a n
- Borthwick, Jennifer A.,Alemparte, Carlos,Wall, Ian,Whitehurst, Benjamin C.,Argyrou, Argyrides,Burley, Glenn,De Dios-Anton, Paco,Guijarro, Laura,Monteiro, Maria Candida,Ortega, Fatima,Suckling, Colin J,Pichel, Julia Castro,Cacho, Monica,Young, Robert J.
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p. 2557 - 2576
(2020/03/31)
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- Regioselective metalations of pyrimidines and pyrazines by using frustrated Lewis pairs of BF3×OEt2 and hindered magnesium- and zinc-amide bases
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Born of frustration: Using the frustrated Lewis pairs TMP-metal and BF 3×OEt2 allows the regioselective metalation of pharmaceutically relevant diazines, such as pyrimidines, purines, and pyrazines. These metalations are often complementary to prior deprotonations performed without BF3×OEt2. Especially attractive is a new sequential regioselective full functionalization of the pyrazine scaffold with a bulky (TMS)2CH substituent. Copyright
- Groll, Klaus,Manolikakes, Sophia M.,Du Jourdin, Xavier Mollat,Jaric, Milica,Bredihhin, Aleksei,Karaghiosoff, Konstantin,Carell, Thomas,Knochel, Paul
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supporting information
p. 6776 - 6780
(2013/07/26)
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- Effect of substituent structure on pyrimidine electrophilic substitution
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In an investigation into the electrophilic nitrosation reactions of a series of 4,6-disubstituted pyrimidine derivatives, a subtle interplay between the electronic nature of the C-4 and C-6 substituents and reactivity was found where these were chloro-, mono- or disubstituted amino groups. Effects such as the presence of an aryl group or two alkyl groups on the amino moiety impede the progress of the reaction despite the presence of a second activating group.
- van der Westhuyzen, Christiaan W.,Rousseau, Amanda L.,Parkinson, Christopher J.
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p. 5394 - 5405
(2008/01/07)
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- PYRIMIDINE DERIVATIVES AND METHODS OF TREATMENT RELATED TO THE USE THEREOF
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The present invention encompasses novel substituted pyrimidine compounds of Formula (I): which act as MCH receptor antagonists. These compounds are useful in pharmaceutical compositions whose use includes prophylaxis or treatment of improving memory function, sleeping and arousal, anxiety, depression, mood disorders, seizure, obesity, diabetes, appetite and eating disorders, cardiovascular disease, hypertension, dyslipidemia, myocardial infarction, binge eating disorders including bulimia, anorexia, mental disorders including manic depression, schizophrenia, delirium, dementia, stress, cognitive disorders, attention deficit disorder, substance abuse disorders and dyskinesias including Parkinson’s disease, epilepsy, and addiction.
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Page/Page column 106
(2008/06/13)
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