71083-06-2

Usage

InChI:InChI=1/C7H6ClF/c8-7(9)6-4-2-1-3-5-6/h1-5,7H

Upstream product

• 63010-68-4 diethyl [(2-fluoroanilino)methylidene]malonate 
• 348-54-9 2-Fluoroaniline 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 13937-11-6 diethyl butylidenemalonate 
• 70145-31-2 ethyl 2-carboethoxy-3-ethoxy-2-propenecarboxylate 
• 105-53-3 diethyl malonate 

Downstream Products

• 1435910-89-6 ethyl 8-fluoro-1-(oxiran-2-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1207748-36-4 ethyl N-benzyl-8-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1207749-45-8 C₁₉H₁₅BrFNO₃ 
• 71082-99-0 8-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 
• 934000-16-5 8-fluoroquinolin-4(1H)-one 

Relevant academic research and scientific papers

3-(Benzo[: D] thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase i inhibitor via DNA intercalation: Design, synthesis, and antitumor activities

Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate with a low IC50 value of about 2.20 ± 0.14 and was selected for further exploration. Spectroscopic analyses and agarose-gel electrophoresis assays indicated that 5a could interact with DNA and strongly inhibit topoisomerase I (Topo I). Further screening of the Topo I activity of compounds 5b, 5c, 5e, 5f, 5h, 5i, 5j, 5l, and 5n suggested that some of the compounds might exert quite a different cytotoxicity profile to that of 5a. Molecular modeling studies confirmed that 5a adopts a unique mode to interact with DNA and Topo I. Other molecular mechanistic studies suggested that the treatment of MGC-803 cells with 5a induces S phase arrest, up-regulates the pro-apoptotic protein, down-regulates the anti-apoptotic protein, activates caspase-3, and subsequently induces mitochondrial dysfunction so as to induce cell apoptosis. The in vivo efficiency of 5a was also evaluated on MGC-803 xenograft nude mice and the relative tumor growth inhibition was 42.4percent at 12 mg kg-1 without an obvious loss in the body weight. This journal is

Novel BQCA- and TBPB-Derived M1 Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism

Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M1-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M1 positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.

A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy

The investigation of the mode and time course of the activation of G-protein-coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M) receptors, is still in its infancy despite the tremendous therapeutic relevance of M receptors and GPCRs in general. We herein made use of a dualsteric ligand that can concomitantly interact with the orthosteric, that is, the neurotransmitter, binding site and an allosteric one. We synthetically incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized the photophysical properties of this ligand called BQCAAI and investigated its applicability as a pharmacological tool compound with a set of FRET techniques at the M1 receptor. BQCAAI proved to be an unprecedented molecular tool; it is the first photoswitchable dualsteric ligand, and its activity can be regulated by light. We also applied BQCCAI to investigate the time course of several receptor activation processes.

Rational design of partial agonists for the muscarinic M1 acetylcholine receptor

Aiming to design partial agonists for a G-protein-coupled receptor based on dynamic ligand binding, we synthesized three different series of bipharmacophoric ligands composed of the orthosteric building blocks iperoxo and 1 linked to allosteric modulators (BQCA-derived compounds, BQCAd; TBPB-derived compound, TBPBd). Their interactions were studied with the human muscarinic acetylcholine M1-receptor (hM1) with respect to receptor binding and Gq-protein signaling. Results demonstrate that iperoxo/BQCAd (2, 3) and 1/BQCAd hybrids (4) act as M1 partial agonists, whereas 1/TBPBd hybrids (5) did not activate M1-receptors. Among the iperoxo/BQCAd-hybrids, spacer length in conjunction with the pattern of substitution tuned efficacy. Most interestingly, a model of dynamic ligand binding revealed that the spacer length of 2a and 3a controlled the probability of switch between the inactive purely allosteric and the active bitopic orthosteric/allosteric binding pose. In summary, dynamic ligand binding can be exploited in M1 receptors to design partial agonists with graded efficacy.

Regiocontrolled Nitration of 4-Quinolones at Ambient Conditions

Regiocontrolled nitration of 4-quinolone, the highly privileged scaffold, has been developed at ambient conditions. The nitro group can selectively be introduced at diverse positions simply by tuning the reactivity of the moiety. Discrimination is being achieved through the selective functionalization of the free N-H group. The functional group has been screened theoretically with the help of Fukui function and local softness calculation. Theoretical predictions are synchronized well with the experimental findings. Finally, this nitration technique allows quick access to the structurally diverse 4-quinolones.

Synthesis of 6-aryl substituted 4-quinolones via Suzuki cross coupling

A convenient way to introduce aryl functionalization in the 6-position of 4-quinolones is developed via selective bromination and subsequent arylation by Suzuki cross-coupling. Ethyl 4-quinolone 3-carboxylates were subjected to selective bromination at C-6 followed by arylation under microwave irradiation that yielded the desired cross-coupling products within 5 minutes. This approach can expediently be used for library synthesis of the aryl functionalized 4-quinolone derivative, an important class of biologically active compounds.

Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin

A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg2+ ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.

Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV-vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b-DNA complex which might block DNA replication and thus exert its antimicrobial activities.

QUINOLINE DERIVATIVES AS CASPASE-3 INHIBITOR, PREPARATION PROCESS FOR THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Provided is a quinoline derivative represented by the following Formula (1) for use in treating a caspase- mediated disease by inhibition of caspase-3 activity. Further provided are a method for preparing the quinoline derivative or a pharmaceutically acceptable salt thereof and a pharmaceutical composition containing the same.

Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2

Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitors-3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC 50 = 0.3 μM) and 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (9) (IC50 = 1 μM), are ATP competitive (Ki values are 0.06 and 0.28 μM, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.