849235-68-3Relevant articles and documents
Synthesis, Biological Activities and Docking Studies of Novel 4-(Arylaminomethyl)benzamide Derivatives as Potential Tyrosine Kinase Inhibitors
Kalinichenko, Elena,Faryna, Aliaksandr,Kondrateva, Viktoria,Vlasova, Alena,Shevchenko, Valentina,Melnik, Alla,Avdoshko, Olga,Belko, Alla
, (2019/10/03)
A number of new compounds containing the 4-(aminomethyl)benzamide fragment as a linker were designed and synthesized, and their biological activities were evaluated as potential anticancer agents. The cytotoxicity activity of the designed compounds was studied in two hematological and five solid cell lines in comparison with the reference drugs. Targeted structures against eight receptor tyrosine kinases including EGFR, HER-2, HER-4, IGF1R, InsR, KDR, PDGFRa, and PDGFRb were investigated. The majority of the compounds showed a potent inhibitory activity against the tested kinases. The analogues 11 and 13 with the (trifluoromethyl)benzene ring in the amide or amine moiety of the molecule were proven to be highly potent against EGFR, with 91% and 92% inhibition at 10 nM, respectively. The docking of synthesized target compounds for nine protein kinases contained in the Protein Data Bank (PDB) database was carried out. The molecular modeling results for analogue 10 showed that the use of the 4-(aminomethyl)benzamide as a flexible linker leads to a favorable overall geometry of the molecule, which allows one to bypass the bulk isoleucine residue and provides the necessary binding to the active center of the T315I-mutant Abl (PDB: 3QRJ).
Navigating into the chemical space between MGCD0103 and SAHA: Novel histone deacetylase inhibitors as a promising lead
Zhang, Xin,Lv, Peng-Cheng,Li, Dong-Dong,Zhang, Wei-Ming,Zhu, Hai-Liang
, p. 1816 - 1825 (2015/10/20)
Histone deacetylase inhibitors (HDIs) are an increasingly important class of cancer-targeting agents. Two kinds of small molecule histone deacetylase inhibitors, mainly employing the motifs of the two known HDAC inhibitors MGCD0103 and SAHA as the basic scaffolds, were designed, synthesized and evaluated for the preliminary biological activity. Strikingly, these two compounds regained a long half-life potency like MGCD0103 and retained the non-selectivity for HDAC1 versus HDAC6 derived from SAHA. Together, these two compounds combining both the advantages of MGCD0103 and SAHA could be considered as novel histone deacetylase inhibitors in targeted drug development and possibly anticipated to be more effective under the clinical trials.
PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIMIDINES
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Paragraph 0280, (2015/02/02)
This invention relates to an improved process of making compounds of Formula (I) and synthetic intermediates thereof. (I) In particular, the invention relates to an improved process to prepare N-(2-aminophenyl)-4- ((pyrimidin-2-ylamino)methyl)benzamides which requires fewer steps, is efficient, can be used on an industrial scale, and results in a final product which is suitable for pharmaceutical use.
Discovery of potent, isoform-selective inhibitors of histone deacetylase containing chiral heterocyclic capping groups and a N-(2-aminophenyl)benzamide binding unit
Marson, Charles M.,Matthews, Christopher J.,Yiannaki, Elena,Atkinson, Stephen J.,Soden, Peter E.,Shukla, Lena,Lamadema, Nermina,Thomas, N. Shaun B.
, p. 6156 - 6174 (2013/09/02)
The synthesis of a novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contain a heterocyclic capping group and a N-(2-aminophenyl)benzamide unit that binds in the active site. In vitro assays for the inhibition of HDAC1, HDAC2, HDAC3-NCoR1, and HDAC8 by the N-(2-aminophenyl)benzamide 24a gave respective IC50 values of 930, 85, 12, and 4100 nM, exhibiting class I selectivity and potent inhibition of HDAC3-NCoR1. Both imidazolinone and thiazoline rings are shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl) benzamides previously reported, an example of each ring system at 1 μM causing an increase in histone H3K9 acetylation in the human cell lines Jurkat and HeLa and an increase in cell death consistent with induction of apoptosis. Inhibition of the growth of MCF-7, A549, DU145, and HCT116 cell lines by 24a was observed, with respective IC50 values of 5.4, 5.8, 6.4, and 2.2 mM.
Discovery of N-(2-Aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino) methyl]benzamide(MGCD0103), an orally active histone deacetylase inhibitor
Zhou, Nancy,Moradei, Oscar,Raeppel, Stephane,Leit, Silvana,Frechette, Sylvie,Gaudette, Frederic,Paquin, Isabelle,Bernstein, Naomy,Bouchain, Giliane,Vaisburg, Arkadii,Jin, Zhiyun,Gillespie, Jeff,Wang, James,Fournel, Marielle,Yan, Pu T.,Trachy-Bourget, Marie-Claude,Kalita, Ann,Lu, Aihua,Rahil, Jubrail,MacLeod, A. Robert,Li, Zuomei,Besterman, Jeffrey M.,Delorme, Daniel
scheme or table, p. 4072 - 4075 (2009/05/27)
The design, synthesis, and biological evaluation of N-(2-aminophenyl)-4- [(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide 8 (MGCD0103) is described. Compound 8 is an isotype-selective small molecule histone deacetylase (HDAC) inhibitor that selectively inhibits HDACs 1-3 and 11 at submicromolar concentrations in vitro. 8 blocks cancer cell proliferation and induces histone acetylation, p21ciP/waf1 protein expression, cell-cycle arrest, and apoptosis. 8 is orally bioavailable, has significant antitumor activity in vivo, has entered clinical trials, and shows promise as an anticancer drug.
