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InChI:InChI=1/C10H5ClFNO/c11-10-7(5-14)3-6-4-8(12)1-2-9(6)13-10/h1-5H

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• 351-83-7 4'-fluoroacetanilide 
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• 326-65-8 N-(4-fluoro-2-methylphenyl)acetamide 
• 371-40-4 4-fluoroaniline 

Relevant academic research and scientific papers

Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules

A new series of quinolone-thiazolidinone hybrid molecules 8a-o were prepared. Quinoline compounds were synthesized by Meth-Cohn synthesis and were condensed with 2,3-disubstituted thiazolidinone. These molecules were screened for their anticancer activities against MDA-MB-231 and MCF-7 cell line using MTT assay. Potent compounds were tested for their cytotoxicity on normal HEK 293 cell lines and most potent compound was tested for its cell cycle analysis. Molecular docking and molecular dynamic studies were performed on human N-acetyl transferase (hNAT-1) protein using Schrodinger molecular docking toolkit. Compound 8n emerged as potent with IC50 8.16?μM against MDA-MB-231 cell line followed by 8e with IC50 17.68?μM. Compound 8n arrested cell cycle at G2/M phase and was non-toxic to human normal kidney cell line. The potent compound 8n binds well with human NAT-1 protein with remarkable hydrogen bonding and π–π interactions. Molecular dynamic studies of 8n further confirm the target for these molecules. Target quinolinone-thiazolidinones were found to be new class of compounds targeting hNAT-1 and can serve as new lead compounds in drug discovery.

Design, synthesis and biological evaluation of mono- and bisquinoline methanamine derivatives as potential antiplasmodial agents

Several classes of antimalarial drugs are currently available, although issues of toxicity and the emergence of drug resistant malaria parasites have reduced their overall therapeutic efficiency. Quinoline based antiplasmodial drugs have unequivocally been long-established and continue to inspire the design of new antimalarial agents. Herein, a series of mono- and bisquinoline methanamine derivatives were synthesised through sequential steps; Vilsmeier-Haack, reductive amination, and nucleophilic substitution, and obtained in low to excellent yields. The resulting compounds were investigated for in vitro antiplasmodial activity against the 3D7 chloroquine-sensitive strain of Plasmodium falciparum, and compounds 40 and 59 emerged as the most promising with IC50 values of 0.23 and 0.93 μM, respectively. The most promising compounds were also evaluated in silico by molecular docking protocols for binding affinity to the {0 0 1} fast-growing face of a hemozoin crystal model.

Arylquinolinecarboxamides: Synthesis, in vitro and in silico studies against Mycobacterium tuberculosis

A series of fourteen 6-substituted-2-(methoxyquinolin-3-yl) methyl)-N-(pyridin-3-ylmethyl) benzamides was prepared from commercially available anilines in five simple and convenient synthetic steps. The structures of all new products were confirmed by routine spectroscopic methods: IR, 1H and 13C NMR, and HRMS (electrospray ionization). The resulting arylquinolinecarboxamides were subjected to biological screening assay for in vitro inhibitory activity against Mycobacterium tuberculosis (Mtb) H37Rv strain. Several compounds exhibited modest antitubercular activity with compounds 8–11, 15 and 19 exhibiting MIC90 values in the range of 32–85 μM. The antitubercular data suggested that inhibition of Mtb can be imparted by the introduction of a non-polar substituent on C-6 of the quinoline scaffold. Further, to understand the possible mode of action of the series, the reported compounds and bedaquiline were subjected to in silico docking studies against MtbATPase to determine their potential to interfere with the mycobacterial adenosine triphosphate (ATP) synthase. The results showed that these compounds have the potential to serve as antimycobacterial agents. In silico ADME pharmacokinetic prediction results showed the ability of these arylquinolinecarcboxamides to be absorbed, distributed, metabolized and excreted efficiently.

Enantioselective synthesis of functionalized 1,4-dihydropyrazolo-[4′,3′:5,6]pyrano[2,3-: B] quinolines through ferrocenyl-phosphine-catalyzed annulation of modified MBH carbonates and pyrazolones

An enantioselective synthesis of highly functionalized 1,4-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolines from modified MBH carbonates and pyrazolones via a chiral phosphine-mediated alkylation/annulation sequence has been realized. The chiral dihydropyrano[2,3-c]pyrazoles bearing bio-active condensed heterocycles were facilely formed in good chemical yields and with high to excellent enantioselectivity by utilizing low catalyst loading.

Synthesis of indenoquinolinone through aryne-mediated Pd(II)-catalysed remote C–H activation

Abstract: [Figure not available: see fulltext.]Indenoquinolinones have been synthesized from 2-haloquinoline-3-carbaldehyde through Pd-mediated simultaneous C–H (aldehyde) and C–X bond activation. DFT studies were performed to investigate the mechanistic pathway, and in situ UV–Vis studies indicate the presence of Pd(II) intermediate species. Aryne ligated Pd complex is actual intermediate in these reactions. Ligation of reactive aryne to Pd reduces probability of side reactions. Graphic abstract: [Figure not available: see fulltext.]

IMIDAZOPIPERAZINONE INHIBITORS OF TRANSCRIPTION ACTIVATING PROTEINS

The present disclosure relates to heterocyclic compounds and methods which may be useful as inhibitors of transcription activating proteins such as CBP and P300 for the treatment or prevention of diseases such as proliferative diseases, inflammatory disorders, autoimmune diseases, and fibrotic diseases.

Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors

Urea transporters (UTs) play an important role in the urine concentrating mechanism and are recognized as novel targets for developing small molecule inhibitors with salt-sparing diuretic activity. Thienoquinoline derivatives, a class of novel UT-B inhibitors identified by our group, play a significant diuresis in animal model. However, the poor solubility and low bioavailability limited its further development. To overcome these shortcomings, the structure modification of thienoquinoline was carried out in this study, which led to the discovery of novel thienopyridine derivatives as specific urea transporter inhibitors. Further optimization obtained the promising preclinical candidate 8n with not only excellent inhibition effect on urea transporters and diuretic activity on rat model, but also suitable water solubility and Log P value.

Synthesis, antibacterial activity and docking studies of substituted quinolone thiosemicarbazones

Fifteen 2-quinolone thiosemicarbazone derivatives of which eleven were new, were synthesized at room temperature. The key intermediate was the quinolone carbaldehyde, from which thiosemicarbazones were formed by the reaction of thiosemicarbazides with the aldehyde moiety. The structures of the synthesized compounds were elucidated by 1D and 2D-NMR spectroscopy and mass spectrometry. The synthesized compounds showed antibacterial activity with MBCs in the range 0.80 to 36.49 mM against Staphylococcus aureus, Staphylococcus aureus Rosenbach (MRSA), Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Salmonella typhimurium. The best activity was seen when a larger halogen such as chlorine and bromine were substituted at C-6 on the quinolone scaffold and when a planar phenyl group was present on the thiosemicarbazone moiety. Activity was reduced when a smaller fluorine atom was present at C-6 or when a methyl group was attached to the thiosemicarbazone. This group of compounds showed a high negative binding affinity, which suggested promising antimcrobial activity. The 6-chloro derivative with a phenyl group on the thiosemicarbazone had the greatest negative binding affinity.

Synthesis and Bioactivity of Quinoline-3-carboxamide Derivatives

Twelve novel substituted 2-chloroquinoline-3-carboxamide derivatives were prepared from acetanilides using the Vilsmeier–Haack reaction, producing 2-chloro-3-carbaldehyde quinolines, followed by oxidation of the 3-carbaldehyde to the carboxylic acid and coupling this group with various anilines. The structures of the synthesized compounds were confirmed by NMR, mass spectrometry, and single crystal X-ray diffraction. The chemical shifts of H-5 and H-8 were shown to be influenced by the substituent at C-6. The substituent at C-6 was also seen to affect the chemical shift of C-5, C-7, and C-8, with C-5 and C-7 being more shielded in 5j (F substituted) in comparison with 5g (Cl substituted) and 5d (CH3 substituted). The compounds showed weak activity in the mM range against Gram-positive and Gram-negative bacteria of which 5b, 5d, and 5f showed the best activity with minimum bactericidal concentration values for 5b being 3.79?mM against methicillin-resistant Staphylococcus aureus and 5d and 5f having minimum bactericidal concentration values of 3.77 and 1.79?mM against S.?aureus ATCC 25923, respectively.

Tetrazolylmethyl quinolines: Design, docking studies, synthesis, anticancer and antifungal analyses

A new series of 2,5 and 1,5-regioisomers of the tetrazolyl group viz., 3-[(5-benzyl/benzylthio-2H-tetrazol-2-yl) methyl]-2-chloro-6-substituted quinoline 6h-q and 3-[(5-benzyl/benzylthio-1H-tetrazol-1-yl) methyl]-2-chloro-6-substituted quinolines 7h-q were synthesized. Docking studies of all these compounds with DNA as target using PDB: 1AU5 and 453D revealed that the compounds 6h and 6i act as covalent cross linker on the DNA helix of the former and intercalate the latter both with higher C score values. Another set of docking studies in the active pocket of dihydrofolate reductase and N-myristoyl transferase as targets to assess antifungal activity revealed that compounds 6k, 6l, 6p and 7q (with bromo and fluro substituents) showcases different binding modes and hydrogen bonding. Further, the compounds were screened for anticancer activity (primary cytotoxicity) against NCI-60 Human tumor cell line at a single high dose (10?5M) concentration assay. Among the tested compounds, 6h has shown 99.28% of GI against Melanoma (SK-MEL-5) and compound 6i has shown 97.56% of GI against Breast Cancer (T-47D). Further, in vitro antifungal assay against A. fumigatus and C. albicans for these compounds 6h-q and 7h-q revealed potential to moderate activities as compared to the standard.