342899-34-7Relevant academic research and scientific papers
SMALL MOLECULE INHIBITORS OF NF-kB INDUCING KINASE
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Page/Page column 127, (2020/12/11)
The present invention relates to compounds that inhibit NIK and pharmaceutical compositions comprising such compounds and methods of using the same. These compounds and pharmaceutical compositions are envisaged to be useful for preventing or treating diseases such as cancer (such as B-cell malignancies including leukemias, lymphomas and myeloma), inflammatory disorders, autoimmune disorders, immunodermatologic disorders such as palmoplantar pustulosis and hidradenitis suppurativa, and metabolic disorders such as obesity and diabetes.
Design, Synthesis and Characterization of Covalent KDM5 Inhibitors
Vazquez-Rodriguez, Saleta,Wright, Miranda,Rogers, Catherine M.,Cribbs, Adam P.,Velupillai, Srikannathasan,Philpott, Martin,Lee, Henry,Dunford, James E.,Huber, Kilian V. M.,Robers, Matthew B.,Vasta, James D.,Thezenas, Marie-Laetitia,Bonham, Sarah,Kessler, Benedikt,Bennett, James,Fedorov, Oleg,Raynaud, Florence,Donovan, Adam,Blagg, Julian,Bavetsias, Vassilios,Oppermann, Udo,Bountra, Chas,Kawamura, Akane,Brennan, Paul E.
supporting information, p. 515 - 519 (2018/12/14)
Histone lysine demethylases (KDMs) are involved in the dynamic regulation of gene expression and they play a critical role in several biological processes. Achieving selectivity over the different KDMs has been a major challenge for KDM inhibitor development. Here we report potent and selective KDM5 covalent inhibitors designed to target cysteine residues only present in the KDM5 sub-family. The covalent binding to the targeted proteins was confirmed by MS and time-dependent inhibition. Additional competition assays show that compounds were non 2-OG competitive. Target engagement and ChIP-seq analysis showed that the compounds inhibited the KDM5 members in cells at nano- to micromolar levels and induce a global increase of the H3K4me3 mark at transcriptional start sites.
Substituted Quinazoline and Pyridopyrimidine Derivatives Useful as Anticancer Agents
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Paragraph 0170; 0171, (2019/08/22)
Compounds of the general formula: processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
Synthesis of Novel Hydroxymethyl-Substituted Fused Heterocycles
Holmes, Jane L.,Almeida, Lynsie,Barlaam, Bernard,Croft, Rosemary A.,Dishington, Allan P.,Gingipalli, Laksmaiah,Hassall, Lorraine A.,Hawkins, Janet L.,Ioannidis, Stephanos,Johannes, Jeffrey W.,McGuire, Thomas M.,Moore, Jane E.,Patel, Anil,Pike, Kurt G.,Pontz, Timothy,Wu, Xiaoyun,Wang, Tao,Zhang, Hai-Jun,Zheng, Xiaolan
, p. 1226 - 1234 (2016/05/19)
Examples of hydroxymethylated analogues of heteroaryl cores such as quinazolin-4-ones, isoquinolin-1(2H)-ones, pyrido[3,4-d]pyrimidin-4(3H)-ones, chromen-4-ones and pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones are sparse or non-existent in the scientific literature. We have demonstrated that such compounds are accessible by using standard procedures from readily available raw materials.
8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors
Bavetsias, Vassilios,Lanigan, Rachel M.,Ruda, Gian Filippo,Atrash, Butrus,McLaughlin, Mark G.,Tumber, Anthony,Mok, N. Yi,Le Bihan, Yann-Va?,Dempster, Sally,Boxall, Katherine J.,Jeganathan, Fiona,Hatch, Stephanie B.,Savitsky, Pavel,Velupillai, Srikannathasan,Krojer, Tobias,England, Katherine S.,Sejberg, Jimmy,Thai, Ching,Donovan, Adam,Pal, Akos,Scozzafava, Giuseppe,Bennett, James M.,Kawamura, Akane,Johansson, Catrine,Szykowska, Aleksandra,Gileadi, Carina,Burgess-Brown, Nicola A.,Von Delft, Frank,Oppermann, Udo,Walters, Zoe,Shipley, Janet,Raynaud, Florence I.,Westaway, Susan M.,Prinjha, Rab K.,Fedorov, Oleg,Burke, Rosemary,Schofield, Christopher J.,Westwood, Isaac M.,Bountra, Chas,Müller, Susanne,Van Montfort, Rob L. M.,Brennan, Paul E.,Blagg, Julian
, p. 1388 - 1409 (2016/03/05)
We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay.
Preparation of 4-substituted 3-amino-2-chloropyridines, synthesis of a nevirapine analogue
Bakke,Riha
, p. 99 - 104 (2007/10/03)
A new method for preparing 3-amino-2-chloropyridines with a substituent (methyl, phenyl, carboxamide, methoxycarbonyl, acetyl, benzoyl and cyano) at the 4-position has been developed. An isoquinoline analogue of the reverse transcriptase inhibitor Nevirapine has been synthesized from the 4-amino-3-chloroisoquinoline.
