Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors

Liao, Weike; Xu, Chen; Ji, Xiaohui; Hu, Gang; Ren, Lixiang; Liu, Yajing; Li, Ruijuan; Gong, Ping; Sun, Tiemin

doi:10.1016/j.ejmech.2014.09.095

Cited by 25 publications

(11 citation statements)

References 17 publications

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“…Adamantane derivatives were early known for their diverse chemotherapeutic activities such as antiviral [3][4][5][6][7][8][9], anticancer [10] and antibacterial [11][12][13][14] agents. In addition, several hydrazide and hydrazine derivatives were reported to possess marked antifungal [15,16], antileishmanial [17,18] and anticancer [19,20] activities. In continuation to our ongoing interest in the structural and pharmacological properties of adamantane derivatives [8,[11][12][13], we synthesized the title compound as potential and/or precursor to chemotherapeutic agent.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C₁₆H₁₉N₃O

Al-Tamimi

Ghabbour²,

El-Emam

2016

Zeitschrift Für Kristallographie - New Crystal Structures

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CCDC no.: 1420126The crystal structure is shown in the gure. Tables 1-3 contain details of the measurement method and a list of the atoms including atomic coordinates and displacement parameters. Source of materialA mixture of 2-adamantanone (1.5 g, 0.01 mol) and pyridine-3-carbohydrazide (1.37 g, 0.01 mol), in ethanol (10 ml) was heated under re ux with stirring for 4 h and the resulted clear solution was then concentrated to half the original volume and allowed to stand at room temperature overnight. The precipitated crystalline solid was ltered, dried and recrystallized from aqueous ethanol to yield 1.78 g (66%)

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Section: Discussionmentioning

confidence: 99%

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C₁₆H₁₉N₃O

Al-Tamimi

Ghabbour²,

El-Emam

2016

Zeitschrift Für Kristallographie - New Crystal Structures

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“…In the last few years, a lot of more active and selective quinoline derivatives have been synthesized and biologically evaluated by modifying lead compounds ( Table 1 ). The most representative modifications are: (1) at position C-7 of quinoline ring system, generally with the introduction of appropriate substituents to improve solubility, (2) at the linker portion [ 34 ], that has been modified by different cyclic/acyclic 5-atoms-analogues with similar electronic features: pyridazinone-3-carboxyamide 3 [ 35 ], 3-oxo-3,4-dihydroquinoxaline 4 [ 36 ], 1H-imidazole-4-carboxamide or (E)-3-hydrosulfonylacrylamide 5 , 6 [ 37 ], 1,2,3-triazole-4-carboxamide 7 , 8 [ 38 , 39 ], 2-imidazolone-4-carboxamide 9 [ 40 ], acylhydrazone moiety 10 [ 41 ], pyridine/pyrimidine-2-carboxyamide 11 [ 42 ], 2-phenylquinoline-4-carboxamide 12 [ 33 ], 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety 13 [ 43 ], acyclic semicarbazones 14 [ 44 , 45 ], acylthiourea moiety [ 46 ], l,2,4-triazine-3,5-dione 15 [ 47 ], 1,8-naphthyridin-2-one 16 [ 48 ], 2-oxo-1,2-dihydropiridine-3-carboxamide 17 [ 49 ], 4-oxo-1,4-dihydroquinoline-3-carboxamide 18 [ 50 ], 5-(aminomethylene)pyrimidine-2,4,6-trione moiety 19 [ 51 ], 4-oxo-3,4-dihydrophthalazine-1-carboxamide 20 [ 52 ], pyrazolone 21 [ 53 ], and (thio)semicarbazone 22 [ 54 ].…”

Section: Quinolines As Inhibitors Of Carcinogenic Pathwaysmentioning

confidence: 99%

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

2020

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The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as antiproliferative drugs, this review is focused on compounds effective on c-Met, VEGF (vascular endothelial growth factor), and EGF (epidermal growth factor) receptors, pivotal targets for the activation of important carcinogenic pathways (Ras/Raf/MEK and PI3K/AkT/mTOR). These signalling cascades are closely connected and regulate the survival processes in the cell, such as proliferation, apoptosis, differentiation, and angiogenesis. The antiproliferative biological data of remarkable quinoline compounds have been analysed, confirming the pivotal importance of this ring system in the efficacy of several approved drugs. Furthermore, in view of an SAR (structure-activity relationship) study, the most recurrent ligand–protein interactions of the reviewed molecules are summarized.

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“…derivatives, numerous derivatives were developed and proved to be superior to their prototype drugs [3][4][5][6][7][8]. In addition, various hydrazide and hydrazine analogues were proved to possess potent antibacterial and antifungal [9][10][11][12], antiviral [13], anticancer [14][15][16], and antileishmanial [17,18] activities. Moreover, adamantane derivatives have long been known for their diverse biological activities and several adamantane-based drugs are currently used as efficient therapeutic agents for the treatment of various pathological disorders [19][20][21].…”

Section: Chemical Synthesismentioning

confidence: 99%

Synthesis and Structure Insights of Two Novel Broad-Spectrum Antibacterial Candidates Based on (E)-N′-[(Heteroaryl)methylene]adamantane-1-carbohydrazides

et al. 2020

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Two new N′-heteroarylidene-1-carbohydrazide derivatives, namely; E-N′-[(pyridine-3-yl)methylidene]adamantane-1-carbohydrazide (1) and E-N′-[(5-nitrothiophen-2-yl)methylidene]adamantane-1-carbohydrazide (2), were produced via condensation of adamantane-1-carbohydrazide with the appropriate heterocyclic aldehyde. Both compounds were chemically and structurally characterized by 1H-NMR, 13C-NMR, infrared and UV-vis spectroscopies, and single crystal X-ray diffraction. The study was complemented with density functional theory calculations (DFT). The results show an asymmetrical charge distribution in both compounds, with the electron density accumulated around the nitrogen and oxygen atoms, leaving the positive charge surrounding the N-H and C-H bonds in the hydrazine group. Consequently, the molecules stack in an antiparallel fashion in the crystalline state, although the contribution of the polar contacts to the stability of the lattice is different for 1 (18%) and 2 (42%). This difference affects the density and symmetry of their crystal structures. Both molecules show intense UV-Vis light absorption in the range 200–350 nm (1) and 200–500 nm (2), brought about by π → π* electronic transitions. The electron density difference maps (EDDM) revealed that during light absorption, the electron density flows within the π-delocalized system, among the pyridyl/thiophene ring, the nitro group, and the N′-methyleneacetohydrazide moiety. Interestingly, compounds 1 and 2 constitute broad-spectrum antibacterial candidates, displaying potent antibacterial activity with minimal inhibitory concentration (MIC) values around 0.5–2.0 μg/mL. They also show weak or moderate antifungal activity against the yeast-like pathogenic fungus Candida albicans.

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Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors

Cited by 25 publications

References 17 publications

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C₁₆H₁₉N₃O

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C₁₆H₁₉N₃O

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

Synthesis and Structure Insights of Two Novel Broad-Spectrum Antibacterial Candidates Based on (E)-N′-[(Heteroaryl)methylene]adamantane-1-carbohydrazides

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Design and optimization of novel 4-(2-fluorophenoxy)quinoline derivatives bearing a hydrazone moiety as c-Met kinase inhibitors

Cited by 25 publications

References 17 publications

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C16H19N3O

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C16H19N3O

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

Synthesis and Structure Insights of Two Novel Broad-Spectrum Antibacterial Candidates Based on (E)-N′-[(Heteroaryl)methylene]adamantane-1-carbohydrazides

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Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C₁₆H₁₉N₃O

Crystal structure of N′-(adamantan-2-ylidene)pyridine-3-carbohydrazide, C₁₆H₁₉N₃O