Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives

Chand, Karam; Prasad, Suchita; Tiwari, Rakesh; Shirazi, Amir Nasrolahi; Kumar, Sumit; Parang, Keykavous; Sharma, Sunil K.

doi:10.1016/j.bioorg.2014.02.001

Cited by 21 publications

(5 citation statements)

References 23 publications

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“…Michael acceptors bearing the chromone core were prepared according to Chand’s procedure . To a stirring solution of 3-formylchromone derivative (1.0 equiv) in pyridine was added malonic acid (1.5 equiv), and the reaction mixture was heated at 115 °C for 1.5 h. After cooling at room temperature, the solvent was removed under reduced pressure, and the crude solid obtained was triturated in cold diethyl ether and filtered.…”

Section: Methodsmentioning

confidence: 99%

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Structure-Based Kinetic Control in a Domino Process: A Powerful Tool Toward Molecular Diversity in Chromone Series

et al. 2017

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Two successive original routes leading to two novel families of polyheterocycles starting from the versatile chromone-based Michael acceptors platform are reported herein. The major aspect of this work is the selective access to these frameworks by changing the course of the domino process involved in their formation. First, enaminochromanones were selectively accessed under uncommon kinetic control. In this study, we showed that the tuning of the selectivity toward the kinetic product could be achieved by key structural modifications of the different reaction partners involved in the domino process. Once selectivity was efficiently controlled, enaminochromanones were ultimately transformed into a more complex family of polyheterocycles containing the pyrrolo-oxazinone framework. Here, the modulation of the domino sequence toward these particularly scarce structures was enabled by a pivotal switch in reactivity induced by aryl-λ-iodanes.

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Section: Methodsmentioning

confidence: 99%

“…1 H NMR (300 MHz, CDCl 3 ): δ H 8.30 (d, J = 7.9 Hz, 1H), 8.14 (s, 1H), 7.76–7.67 (m, 1H), 7.48 (td, J = 8.0, 7.6, 5.1 Hz, 2H), 7.37 (d, J = 23.9 Hz, 1H), 7.28 (s, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H). NMR data are in accordance with those reported in the literature …”

Section: Methodsmentioning

confidence: 99%

Structure-Based Kinetic Control in a Domino Process: A Powerful Tool Toward Molecular Diversity in Chromone Series

et al. 2017

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“…Other acids, such as indole acetic acid, hippuric acid, piperic acid, isonicotinic acid were procured from Sigma-Aldrich. All the amides (9)(10)(11)(12)(13)(14)(15)(16)(17)(20)(21) were obtained in moderate to good yields. …”

Section: Chemistrymentioning

confidence: 96%

“…1) [26] conserved in its structure; the drug is efficacious in imatinib resistant cases [27]. On the basis of above and considering the literature reports discussing Abl-imatinib structural interactions [16,[26][27][28][29][30][31][32], we decided to conjugate the scaffolds based on 2-pyridone [21,33,34], benzopyran-2-one [35], benzopyran-4-one [22,36], indole acetic acid, iso-nicotinic acid, hippuric acid, piperic acid, 2-oxoquinolinacetic acid, 3-oxobenzooxazinacetic acid [37], and trimethoxyphenyl acrylic acid [38], with PPAP moiety to form the amide/cyclic amide derivatives.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives

Manchanda

Parshad

Kumar

et al. 2017

Archiv der Pharmazie

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In view of potent kinase inhibitors for the treatment of myriad human disorders, we synthesized some structurally variant amide/cyclic amide derivatives based on pyridylpyrimidinylaminophenyl amine, the key pharmacophore of the kinase inhibitor drug molecule, imatinib, and evaluated their kinase inhibition potency. Among the various synthesized amides, compound 20, a cyclic amide/pyridin-2(1H)-one derivative, exhibited an IC value comparable to that of the drug imatinib against c-Src kinase, and another compound (14) containing a 2-((4-methyl-2-oxo-2H-chromen-6-yl)oxy)acetamide demonstrated an IC value of 8.39 μM. Furthermore, the constitution of the cyclic amide derivative was confirmed by the single-crystal X-ray diffraction technique. These results may serve as a gateway for developing novel next-generation kinase inhibitors.

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“…Pyridine derivatives have always constituted a subject of great interest due to the ubiquity of pyridine in Nature and the extensive presence in the skeletal backbone of many therapeutic agents. These derivatives were reported to possess cytotoxic [9], and anticancer activities [10,11,12,13,14,15,16,17,18] in addition to topoisomerase I, II [19,20,21] and Src inhibitory activities [22,23,24]. Penclomedine (PEN1, 3,5-dichloro-4,6-dimethoxy-2-trichloromethylpyridine), is an antitumor agent which was selected for clinical development by the NCI based on its selective antitumor activity against certain carcinomas [25].…”

Section: Introductionmentioning

confidence: 99%

New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells

et al. 2016

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Abstract:The synthesis of new 3-cyano-2-substituted pyridines bearing various pharmacophores and functionalities at position 2 is described. The synthesized compounds were evaluated for their in vitro anti-cancer activities on five cancer cell lines using 5-FU as reference compound. The results revealed that the benzohydrazide derivative 9a induced growth inhibition in human breast cancer cell line MCF-7 with an IC 50 value of 2 µM and it showed lower cytotoxicity on MCF-12a normal breast epithelial cells. Additionally, 9a induced apoptotic morphological changes and induced apoptosis in MCF-7 in a dose and time-dependent manner according to an enzyme linked immunosorbent apoptosis assay which is further confirmed by a TUNEL assay. Flow cytometric analysis indicated that 9a arrested MCF-7 cells in the G1 phase, which was further confirmed by increased expression of p21 and p27 and reduced expression of CDK2 and CDK4. Western blot data revealed significant upregulation of the expression of p53, Bax, caspase-3 and down-regulation of Bcl-2, Mdm-2 and Akt. Additionally, 9a increased the release of cytochrome c from mitochondria to cytoplasm which provokes the mitochondrial apoptotic pathway while it showed no significant change on the expression of the death receptor proteins procaspase-8, caspase-8 and FAS. Furthermore, 9a reduced the expression of phospho AKT and β-catenin in dose dependent manner while inhibiting the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). Our findings suggest that compound 9a could be considered as a lead structure for further development of more potent apoptosis inducing agents with anti-metastatic activities.

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Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives

Cited by 21 publications

References 23 publications

Structure-Based Kinetic Control in a Domino Process: A Powerful Tool Toward Molecular Diversity in Chromone Series

Structure-Based Kinetic Control in a Domino Process: A Powerful Tool Toward Molecular Diversity in Chromone Series

Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives

New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells

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