8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors was written by Bavetsias, Vassilios;Lanigan, Rachel M.;Ruda, Gian Filippo;Atrash, Butrus;McLaughlin, Mark G.;Tumber, Anthony;Mok, N. Yi;Le Bihan, Yann-Vai;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;Muller, Susanne;van Montfort, Rob L. M.;Brennan, Paul E.;Blagg, Julian. And the article was included in Journal of Medicinal Chemistry in 2016.Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid The following contents are mentioned in the article:
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-Me 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 vs. 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. This study involved multiple reactions and reactants, such as 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid).
3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid (cas: 1373422-53-7) belongs to pyrimidine derivatives. Pyrimidines are isomeric with two other forms of diazines: pyridazine, with the nitrogen atoms in the 1 and 2 positions; and pyrazine, with the nitrogen atoms in the 1 and 4 positions. We all know its importance to life – pyrimidine and purine bases are included in the structure of DNA and RNA.Quality Control of 3-((2-(Pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoic acid
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia