131467-02-2Relevant articles and documents
An Alkynylpyrimidine-Based Covalent Inhibitor That Targets a Unique Cysteine in NF-κB-Inducing Kinase
Al-Khawaldeh, Islam,Al Yasiri, Mohammed J.,Aldred, Gregory G.,Basmadjian, Christine,Bordoni, Cinzia,Harnor, Suzannah J.,Heptinstall, Amy B.,Hobson, Stephen J.,Jennings, Claire E.,Khalifa, Shaimaa,Lebraud, Honorine,Martin, Mathew P.,Miller, Duncan C.,Shrives, Harry J.,de Souza, Jo?o V.,Stewart, Hannah L.,Temple, Max,Thomas, Huw D.,Totobenazara, Jane,Tucker, Julie A.,Tudhope, Susan J.,Wang, Lan Z.,Bronowska, Agnieszka K.,Cano, Céline,Endicott, Jane A.,Golding, Bernard T.,Hardcastle, Ian R.,Hickson, Ian,Wedge, Stephen R.,Willmore, Elaine,Noble, Martin E. M.,Waring, Michael J.
supporting information, p. 10001 - 10018 (2021/07/26)
NF-κB-inducing kinase (NIK) is a key enzyme in the noncanonical NF-κB pathway, of interest in the treatment of a variety of diseases including cancer. Validation of NIK as a drug target requires potent and selective inhibitors. The protein contains a cysteine residue at position 444 in the back pocket of the active site, unique within the kinome. Analysis of existing inhibitor scaffolds and early structure-activity relationships (SARs) led to the design of C444-targeting covalent inhibitors based on alkynyl heterocycle warheads. Mass spectrometry provided proof of the covalent mechanism, and the SAR was rationalized by computational modeling. Profiling of more potent analogues in tumor cell lines with constitutively activated NIK signaling induced a weak antiproliferative effect, suggesting that kinase inhibition may have limited impact on cancer cell growth. This study shows that alkynyl heterocycles are potential cysteine traps, which may be employed where common Michael acceptors, such as acrylamides, are not tolerated.
AMINOPYRIMIDINES AS SYK INHIBITORS
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Page/Page column 55, (2011/07/07)
The present invention provides novel pyrimidine amines of formula (I) which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis.
Synthesis of 4-substituted 2-(4-methylpiperazino)pyrimidines and quinazoline analogs as serotonin 5-HT2A receptor ligands
Saczewski, Jaroslaw,Paluchowska, Aldona,Klenc, Jeffrey,Raux, Elizabeth,Barnes, Samuel,Sullivan, Shannon,Duszynska, Beata,Bojarski, Andrzej J.,Strekowskia, Lucjan
experimental part, p. 1259 - 1265 (2010/03/23)
(Chemical Equation Presented) The addition reaction of lithium reagents to the 4 position of 2-chloropyrimidine or 2-chloroquinazoline followed by oxidation of the resultant dihydro intermediate product is a powerful tool for the synthesis of 4-substitute
