21908-08-7Relevant articles and documents
Selective DIBAL-H Monoreduction of a Diester Using Continuous Flow Chemistry: From Benchtop to Kilo Lab
Uhlig, Nick,Martins, Andrew,Gao, Detian
, p. 2326 - 2335 (2020)
Herein we report a selective DIBAL-H-mediated reduction of a heterocyclic diester to the corresponding monoaldehyde using continuous flow chemistry. The use of continuous flow enabled operation at lower temperatures and better control of the reaction time, thereby allowing for a significant increase in reaction selectivity and yield compared with batch conditions. The reaction's development as a continuous flow process and its scale-up from laboratory gram scale to multikilogram scale are discussed, including design of experiments studies to probe the optimal reaction window.
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)
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.
HISTONE DEMETHYLASE 5 INHIBITORS AND USES THEREOF
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Paragraph 00355; 00357, (2020/03/02)
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the compounds or compositions disclosed herein for treating and/or preventing proliferative diseases, cancers, carcinoma lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, leukemia, sarcoma and/or cardiovascular diseases in a subject in need thereof. In certain embodiments, the sarcoma is Ewing's sarcoma. Provided are methods of inhibiting a histone demethylase in a subject and/or in a cell, tissue, or biological sample. In certain embodiments, the histone demethylase is a KDM. In certain embodiments, the KDM is KDM5. In certain embodiments, the biological sample is a cell. In certain embodiments, the biological sample is a tissue.
MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Paragraph 0090; 0093; 0094, (2016/09/22)
Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with methyl modifying enzymes. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with methyl modifying enzymes.
N-substituted nonaryl-heterocyclo amidyl NMDA/NR2B Antagonists
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, (2008/06/13)
Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are effective as NMDA NR2B antagonists useful for relieving pain.
Cholinesterase reactivators derived from pyridine-2-carbaldoxime
Bielavsky, Jiri,Kassa, Jiri,Elsnerova, Iva,Dejmek, Lubos
, p. 199 - 204 (2007/10/03)
Monoquaternary reactivators of cholinesterase 3a-3c were prepared by quaternization of substituted pyridine-2-carbaldoximes with an ester (1a, 1b) or carbamoyl (2) function in position 4. A new bisquaternary reactivator, 4-carbamoyl-2′-[(hydroxyimino)methyl]-1,1′-(but-2-ene-1,4-diyl) bispyridinium salt (5), was derived from the unsubstituted pyridine-2-carbaldoxime. The compounds were characterized by UV spectra and ionization constants. The substances exhibit antidote effects in intoxications with organophosphate cholinesterase inhibitors.
