Quinolinone Derivatives Research Articles

Tandem chalcone-sulfonamide hybridization, cyclization and further Claisen–Schmidt condensation: Tuning molecular diversity through reaction time and order and catalyst

We here report the synthesis of novel chalcone-sulfonamide compounds based on the hybridization at 2′ position and nitro substitution at the side chalcone phenyl ring followed by tandem cyclization into quinolinone derivatives and then a further aldol condensation only as a function of the reaction time. Therefore, for the first time, we have controlled the sequential preparation of chalcone-sulfonamide hybrids, quinolinones and then (E)-3-ene-2,3-dihydroquinolinones simply stopping reaction over increasing time periods. Furthermore, a new molecular scaffold based on a chalcone-(bis)sulfonamide hybrid has been gotten through changing the sequence of coupling reactions and catalyst. This study means practical and useful ways of constructing in high yields new biologically active compounds bearing diversified molecular scaffolds.

An efficient synthesis of 4H-pyrano quinolinone derivatives catalysed by a versatile organocatalyst tetra-n-butylammonium fluoride and their pharmacological screening.

A new series of indole-based pyranoquinoline derivatives P1–24 has been synthesized by a one-pot cyclocondensation reaction of 2-(4-substituted)phenyl-N-allyl-indole-3-carbaldehydes 1a–d; active methylenes 2a–c; and 4-hydroxy-1-substituted quinolin-2(1H)-one 3a–b catalysed by an organocatalyst tetra-n-butylammonium fluoride (TBAF) in aqueous ethanol. The easy experimental procedure of the reaction leads to excellent yields of pyranoquinoline derivatives. All the compounds were screened against a representative panel of bacteria and fungi. Some of the compounds are found to be equipotent or more potent than standard drugs as evident from the structural activity relationship study.

P-TSA-catalyzed facile and efficient one-pot eco-friendly synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives in aqueous medium

A green and operationally simple approach for the synthesis of novel isoxazolyl amino furo[3,2-c]quinolinone derivatives by a one-pot three-component reaction of 4-amino-3-methyl-5 styrylisoxazoles, aryl glyoxal monohydrates and 4-hydroxy-1-methyl-2-quinolinone using p-TSA as the catalyst in aqueous medium was developed. The protocol proves to be an efficient and an environmentally benign in terms of high yields, operational simplicity, clean reaction profile, compatibility with wide range of substrates, water as a solvent and easy purification.

ZrO2 nano particle catalyzed multi-component synthesis of 3-benzylidene-1-phenylquinoline-2,4(1H,3H)-diones and its antimicrobial activity

Zirconium nanoparticles (ZrO2 NPs) used for the multi-component synthesis of 3-benzylidene-1-phenylquinoline-2,4(1H,3H)-dione derivatives were synthesized starting from easily available reactant molecule such as aryaldehyde 1, diphenyl amine 2, di-ethyl malonate 3 in water–ethanol as green solvent. The ZrO2 NPs gave better yield for the first four cycles of reactions. The characterizations of the ZrO2 NPs were performed by using X-ray diffraction (XRD), infrared spectroscopy (IR), and ultraviolet–visible (UV–vis) absorption spectroscopy. The morphological property revealed the formation of nanoscale particles. They developed a greener path for the synthesis of quinolinone derivatives using ZrO2 NPs and water–ethanol as catalyst and solvent. The expected results reveal the catalytic activity, reaction time, and the reusability of catalyst. All the prepared compounds 4a–4j (Q1–Q11) were evaluated for their antibacterial and antifungal activity. The compounds Q1, Q2, Q3, Q5 Q6, Q7, and Q10 were more potent for antibacterial strains, and Q2, Q3, Q4, Q5 Q7, Q8, and Q10 were potent for C. Albicans—an antifungal strain—compared to ciprofloxacin and miconazole as a standard drug. ZrO2 nanoparticle catalyzed multi-component synthesis of 3-benzylidene-1- phenylquinoline-2,4(1H,3H)-diones and their antimicrobial activity

Concise Synthesis of Quinolinone Derivatives

Concise Synthesis of Quinolinone Derivatives

C6- and C7-Substituted 3,4-dihydro-2(1H)-quinolinones as Inhibitors of Monoamine Oxidase.

Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform. Methods and Findings: To expand on these promising findings and to derive structure-activity relationships, the current study synthesizes a series of 14 3,4-dihydro-2(1H)-quinolinone derivatives. An evaluation of their MAO inhibition properties shows that all derivatives are MAO-B specific with the most potent inhibitor (3a) displaying an IC50 value of 0.0014 µM. Selectivities for MAO-B ranged from 99 to 40 000-fold. Conclusions: It may thus be concluded that substitution of 3,4-dihydro-2(1H)-quinolinone on C6 and C7 with a variety of side chains yields highly potent and selective MAO-B inhibitors, compounds with existing and prospective therapeutic applications.

High-refractive quinolinone-based polymers for ophthalmic devices

Seven novel high refractive index (HRI) acrylic monomers, comprising the quinolinone structural motive, have been synthesized and characterized. Cross-linked homo- as well as copolymers were prepared by photochemical bulk polymerization. The homopolymers show refractive indices at 589 nm (n589) ranging from 1.60 up to 1.68, glass transition temperatures (Tg) from 52 to 76 °C, and Abbe numbers (νAbbe) of 19 to 25. Due to these parameters, the homopolymers are not suitable to be used directly for intraocular lens (IOL) manufacture, but the quinolinone monomers may be used as high refractive index components in copolymers. Potential mixtures were calculated theoretically and one example, a copolymer with PEA and PEGPEA, was prepared and characterized. The experimentally found values were Tg = 24 °C, n589 = 1.593, and νAbbe = 28.3. Interestingly, the quinolinone compound which does not have any spacer between the polymerizable group and the high refractive index group appears to be the most useful one. The lightfastness of the new material fulfills the demands for IOLs. Quinolinone derivatives are promising new comonomers for high refractive index copolymers.

Discovery and structure–activity relationship studies of quinolinone derivatives as potent IL-2 suppressive agents

The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immunosuppressive activity was evaluated by measuring suppression of IL-2 release from activated Jurkat T cells. Optimizing the three side chains around the quinolinone skeleton revealed the most active compound: 11l. This compound exhibits potent inhibitory activity toward IL-2 release in both 12-o-tetradecanoylphorbol-13-acetate (PMA)/A23187 (ionomycin) (IC50=80±10nM) and anti-CD3/CD28-stimulated Jurkat T cells (83% inhibition at 10μM) without cytotoxic effects. Further investigation into the underlying mechanism of 11l indicated the suppression of NF-κB and nuclear factor of activated T cells (NFAT) promoter activities in Jurkat T cells.

SYNTHESIS AND CHARACTERIZATION OF QUINOLINONES AND BIOLOGICAL ACTIVITY OF SOME SELECTIVE COMPOUNDS

Quinolinone is a heterocyclic aromatic organic compound. Quinolinone derivatives are having very much usefulness in current therapeutic applications in medicinal chemistry and pharmacology. This compounds having the bicyclic in nature having the fusion of benzene and pyridine the basic moiety present in quinolinones. It is an important pharmacophore and privileged structure in medicinal chemistry. Chromenoquinolinones, isoquinolinones and 4-quinolinones plays a very important role with plenty of useful therapeutic activities such as: antiulcers, antihypertensives, analgesic, anti-inflammatory, anti-virals, antifungals, anticancers, and antihistaminics. The review of the literature shows that the quinolinones derivatives are outstandingly effective compound and number of reviews available for biochemical and pharmacological studies conformed that their molecules are useful against a wide variety of micro-organisms. Because of their importance, the methods for their synthesis have become a focus of synthetic organic chemists. Therefore in the present review we tried to compile the chemistry of different derivative of substituted quinolinones as well as various pharmacological activities and some of the important methodologies used for the synthesis.

Synthesis and Evaluation of 4-Hydroxy Quinolinone Derivatives as Antioxidants of Lubricating Grease

3-(5-(2.4-dichlorophyenyl)-4.5-dihydro-1H-pyrazol-3-yl)-4hydroxy-1-methylquinolin(1H)-one, 5-((4-hydroxy-8-methyl-2-oxo-1.2-dihydroquinolin-3-yl)methylene)-1-phenyl-2-hioxodihydropyrimidine-4.6(1H.5H)-dione, and 1-butyl-4-hydroxy-3-(5-styryl-4.5-dihydro-1H-pyrazol-3yl)quinolin-2(1H)-one were synthesized and characterized by spectroscopy analysis. These compounds are designated I, II and III, respectively. The antioxidants efficiency of the synthesized compounds in lubricating greases had been investigated using ASTM d-942 and ASTM d-664. The obtained data showed that the total acid number and oxygen pressure drop of these compounds in lubricating greases decrease in the order: Comp.III. < Comp.I. < Comp.II. The antioxidant efficiency of the prepared quinolinones derivatives was discussed. Acceptable correlations were obtained between the obtained oxidation inhibition and the calculated quantum chemical parameters.

Copper(i) catalyzed C(sp2)–N bond formation: synthesis of pyrrolo[3,2-c]quinolinone derivatives

An intramolecular copper-catalyzed direct C(sp2)–H activation/C(sp2)–N bond formation reaction has been developed for the synthesis of pyrrolo[3,2-c]quinolinone derivatives under an oxygen atmosphere. This approach presents an alternative route to the tricyclic core of martinellic acid or martinelline.

One-pot synthesis of fused benzoxazino[1,2,3]triazolyl[4,5-c]quinolinone derivatives and their anticancer activity

Cu/Pd catalyzed one pot synthesis of fused benzoxazino[1,2,3]triazolyl[4,5-c]quinolinone hybrids and their cytotoxic activity against human cancer cell lines MCF-7, HeLa and A-549 is described.

Pd-Catalyzed sequential β-C(sp(3))-H arylation and intramolecular amination of δ-C(sp(2))-H bonds for synthesis of quinolinones via an N,O-bidentate directing group.

The pharmacological importance of 2-quinolinone derivatives is well known. Herein, we developed an effective protocol for the synthesis of 2-quinolinone derivatives by palladium-catalyzed sequential β-C(sp(3))-H arylation and selective intramolecular C(sp(2))-H/N-H amination starting with aryl iodides and carboxylic acids. A novel directing group, glycine dimethylamide, was used in the synthesis. We synthesized various quinolinone derivatives, including 5-substituted quinolinones, which are difficult to obtain using the traditional pathway. The directing group could be easily removed and could be readily transformed into other useful functional groups.

ChemInform Abstract: Synthesis of 2‐Quinolinones Through Palladium(II) Acetate Catalyzed Cyclization of N‐(2‐Formylaryl)alkynamides.

A Pd(OAc)2-catalyzed cyclization of N-(2-formyl­aryl)alkynamides initiated by the oxypalladation of alkynes was developed. The method provides a new approach for the efficient and atom-economical synthesis of 2-quinolinone derivatives.

Synthesis and carbonic anhydrase inhibitory properties of amino acid – coumarin/quinolinone conjugates incorporating glycine, alanine and phenylalanine moieties

N-Protected amino acids (Gly, Ala and Phe) were reacted with amino substituted coumarin and quinolinone derivatives, leading to the corresponding N-protected amino acid–coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against various human (h) isoforms, such as hCA I, hCA II, hCA IV and hCA XII. The quinolinone conjugates were inactive as enzyme inhibitors, whereas the coumarins were ineffective hCA I/II inhibitors (KIs > 50 μM) but were submicromolar hCA IV and XII inhibitors, with inhibition constants ranging between 92 nM and 1.19 μM for hCA IV, and between 0.11 and 0.79 μM for hCA XII. These coumarin derivatives, as many others reported earlier, thus show an interesting selective inhibitory profile for the membrane-bound over the cytosolic CA isoforms.

A Combined Quantitative Structure-Activity Relationship Research of Quinolinone Derivatives as Androgen Receptor Antagonists.

Antiandrogens bicalutamide, flutamide and enzalutamide etc. have been used in clinical trials to treat prostate cancer by binding to and antagonizing androgen receptor (AR). Although initially effective, the drug resistance problem will emerge eventually, which results in a high medical need for novel AR antagonist exploitation. Here in this work, to facilitate the rational design of novel AR antagonists, we studied the structure-activity relationships of a series of 2-quinolinone derivatives and investigated the structural requirements for their antiandrogenic activities. Different modeling methods, including 2D MLR, 3D CoMFA and CoMSIA, were implemented to evolve QSAR models. All these models, thoroughly validated, demonstrated satisfactory results especially for the good predictive abilities. The contour maps from 3D CoMFA and CoMSIA models provide visualized explanation of key structural characteristics relevant to the antiandrogenic activities, which is summarized to a position-specific conclusion at the end. The obtained results from this research are practically useful for rational design and screening of promising chemicals with high antiandrogenic activities.

ChemInform Abstract: The Chemistry and Biological Activity of Heterocycle‐Fused Quinolinone Derivatives: A Review

AbstractReview: [49 refs.

A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1

Four quinolinones (1–4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium crustosum AP2T1. In addition, five new quinolinone derivatives (5–9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC50-24 h of 8.4 μg/mL and 30.7 μg/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.

Synthesis of 2-Quinolinones through Palladium(II) Acetate Catalyzed Cyclization of N-(2-Formylaryl)alkynamides

A Pd(OAc)2-catalyzed cyclization of N-(2-formyl­aryl)alkynamides initiated by the oxypalladation of alkynes was developed. The method provides a new approach for the efficient and atom-economical synthesis of 2-quinolinone derivatives.

Rh-Catalyzed decarbonylative coupling with alkynes via C-C activation of isatins.

Herein we report a [5 + 2 - 1] transformation though catalytic decarbonylative coupling between isatins and alkynes, which provides a unique way to synthesize 2-quinolinone derivatives. A broad range of alkynes can be coupled efficiently with high regioselectivity. This reaction is proposed to go through C-C activation of isatins, followed by decarbonylation and alkyne insertion. Directing group (DG) plays a critical role in this transformation. Assisted by the DG, the C-C cleavage of isatins occurs at room temperature.