- Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide
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FT-IR and FT-Raman spectra of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide were recorded and analyzed experimentally and theoretically. The synthesis, 1H NMR and PES scan results are also discussed. Nonlinear optical behavior of the examined molecule was investigated by the determination of first hyperpolarizability. The calculated HOMO and LUMO energies show the chemical activity of the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. From the MEP it is evident that the negative charge covers the carbonyl group and the positive region is over the NH group. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Molecular docking simulations against targets from Mycobacterium tuberculosis are reported and the results suggest that the compound might exhibit inhibitory activity against PknB.
- Ulahannan, Rajeev T.,Panicker, C. Yohannan,Varghese, Hema Tresa,Musiol, Robert,Jampilek, Josef,Van Alsenoy, Christian,War, Javeed Ahmad,Al-Saadi, Abdulaziz A.
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Read Online
- 4-Hydroxy-2-quinolones. 97. Simple synthesis of the esters of 4-halo-substituted 2-oxo-1,2-dihydroquinoline-3-carboxylic acids
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Short term treatment of 3-ethoxycarbonyl-4-morpholino-2-oxo-1,2- dihydroquinoline with aqueous solutions of hydrohalogen acids leads to the formation of the ethyl esters of 4-halo-substituted 2-oxo-1,2-dihydroquinoline- 3-carboxylic acids. Hydrolysis in HF is possible on extended boiling only to the 4-hydroxy derivative.
- Ukrainets,Sidorenko,Gorokhova,Slobodzyan
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Read Online
- One-step Synthesis of 3-Unsubstituted 4-Hydroxy-2(1H)-Quinoline
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3-Unsubstituted 4-hydroxy-2(1H)-quinolone (DHQ) derivatives were synthesized from aniline derivatives and diethyl malonate at low temperature using AlCl3 as catalyst and Eaton reagent as acidic environment. A reaction mechanism was proposed and elucidated. Different synthetic intermediates are specially prepared or purified and used to understand the reaction and validation mechanism.
- Menglin, Ma,Qingrong, Sun,Weiqing, Yang,Xingyi, Wang,Yinan, Xu
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p. 435 - 441
(2021/11/22)
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- Thiophene quinolone compound as well as preparation method and application thereof
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The invention belongs to the field of medicines, and particularly relates to a thiophene quinolone compound as well as a preparation method and application thereof. The structural formula of the thiophene quinolone compound disclosed by the invention is shown I. The thiophene quinolone compound shown in the formula I is obtained, CDK5 inhibition activity is high, and water solubility is good.
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Paragraph 0070; 0088; 0092-0093
(2021/09/26)
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- Sequential Oxidative Fragmentation and Skeletal Rearrangement of Peroxides for the Synthesis of Quinazolinone Derivatives
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For the first time, the sequential reaction of peroxyoxindole that involves base-promoted oxidative fragmentation to isocyanate formation and primary amine or amino alcohol accelerated skeletal rearrangement to synthesize exo-olefinic-substituted quinazolinone or oxazoloquinazolinone is reported. The advantages of this new reaction include a broad substrate scope and transition-metal-free and room-temperature conditions. The formation of the isocyanate as a key intermediate that accelerates oxidative skeletal rearrangement has been confirmed by trapping experiments and spectroscopic evidence.
- Ubale, Akash S.,Shaikh, Moseen A.,Gnanaprakasam, Boopathy
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p. 9621 - 9636
(2021/07/28)
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- Identification and molecular modeling of new quinolin-2-one thiosemicarbazide scaffold with antimicrobial urease inhibitory activity
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Abstract: A new series of 6-substituted quinolin-2-one thiosemicarbazides 6a–j has been synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analyses. All the designed final compounds were evaluated for their in vitro activity against the urease-producing R. mucilaginosa and Proteus mirabilis bacteria as fungal and bacterial pathogens, respectively. Moreover, all compounds were in vitro tested as potential urease inhibitors using the cup-plate diffusion method. Compounds 6a and 6b were the most active with (IC50 = 0.58 ± 0.15 and 0.43 ± 0.09?μM), respectively, in comparison with lead compound I (IC50 = 1.13 ± 0.00?μM). Also, the designed compounds were docked into urease proteins (ID: 3LA4 and ID: 4UBP) using Open Eye software to understand correctly about ligand–receptor interactions. The docking results revealed that the designed compounds can interact with the active site of the enzyme through multiple strong hydrogen bonds. Moreover, rapid overlay of chemical structures’ analysis was described to understand the 3D QSAR of synthesized compounds as urease inhibitors. The results emphasize the importance of polar thiosemicarbazide directly linked to 6-substituted quinolone moieties as promising antimicrobial urease inhibitors. Graphic abstract: [Figure not available: see fulltext.]
- Elbastawesy, Mohammed A. I.,El-Shaier, Yaseen A. M. M.,Ramadan, Mohamed,Brown, Alan B.,Aly, Ashraf A.,Abuo-Rahma, Gamal El-Din A.
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- Method for preparing 4-hydroxyquinolin-2(1H)-one compound
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The invention discloses a method for preparing a 4-hydroxyquinolin-2(1H)-one compound, which comprises the following steps of: reacting 2-ethynylaniline as shown in a formula (1) and carbon dioxide which are used as raw materials in an ionic liquid in the presence of a silver salt catalyst to obtain the 4-hydroxyquinoline-2 (1H)-one compound as shown in a formula (II). The reaction equation is shown in the specification. When the method disclosed by the invention is applied to the reaction for preparing the 4-hydroxyquinolin-2(1H)-one compound, the reaction conditions are relatively mild, the dosage of the silver salt catalyst is small, the separation and purification process of the product is relatively simple, the product yield is high, and the application range of a substrate is wide.
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Paragraph 0025-0063
(2021/09/22)
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- Preparation method of high-purity 4-hydroxy-quinoline-2 (1H)-ketone
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The invention provides a synthesis method of high-purity 4-hydroxy-quinoline-2 (1H)-ketone. The method comprises the following steps: heating a compound as shown in a general formula (I) in methanesulfonic acid, cooling a reaction solution to 10-30 DEG C after the reaction is finished, adding water to crystallize, separating and drying to obtain a compound as shown in a general formula (II) with the content of 99.0% or above. According to the synthesis method, generation of by-products of the structure shown in the formula (III) is avoided, the tedious post-treatment purification process is reduced, and the synthesis method is suitable for industrial production.
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Paragraph 0005; 0010-0014
(2020/05/08)
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- Method for synthesizing bactericide intermediate
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The invention discloses a method for synthesizing a bactericide intermediate. The method comprises the following steps: adding diethyl malonate into a certain amount of aniline for ammonolysis, addingN1,N3-diphenyl malonamide obtained after ammonolysis into polyphosphoric acid for cyclization, carrying out refining after the reaction is completed to obtain 4-hydroxyquinolin-2(1H)-one, performingan amine methylation reaction to obtain 3-[(phenylamino)methylene]-quinoline-2,4(1H,3H)-dione, performing chlorination hydrolysis on the 3-[(phenylamino)methylene]-quinoline-2,4(1H,3H)-dione to obtaina crude product, and carrying out pulping by toluene to obtain the bactericide intermediate. The method provided by the invention has the advantages of easily available raw materials, low cost, simple operation and high yield, and is suitable for industrial production.
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Paragraph 0006
(2020/01/12)
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- Mild, efficient, and solvent-free synthesis of 4-hydroxy-2-quinolinones
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Malonic acid monoanilides were obtained in excellent yield from the reaction of anilines with Meldrum's acid under solvent-free conditions. The malonic acid monoanilide intermediates were then treated with methanesulfonic acid anhydride (MSAA) to produce 4-hydroxy-2-quinolinones in excellent yield. It should be noted that both reactions had to be run under mild conditions to avoid the decarboxylation of the malonic acid monoanilide intermediate.
- Amagata, Taro,Assad, Meerna Y.,Atalay, Sanberk S.,Wu, Weiming
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- Synthesis and colon anticancer activity of some novel thiazole/-2-quinolone derivatives
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We direct for the synthesis of 1,6,7-trisubstituted-4-phenylthiazol-2(3H)-ylidene)hydrazono)methyl)quinolin-2-one derivatives by the reaction of corresponding thiosemicarbazone derived by 2-quinolone derivatives with 2-bromoacetophenones in presence of triethylamine at room temperature. The mechanism of the formed products was discussed. The structure of the obtained products was fully characterized using different spectral techniques including infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS) together with elemental analyses. The new synthesized compounds showed a moderate colon anticancer activity.
- Aly, Ashraf A.,Mohamed, Asmaa H.,Ramadan, Mohamed
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- Arylidenes of Quinolin-2-one scaffold as Erlotinib analogues with activities against leukemia through inhibition of EGFR TK/ STAT-3 pathways
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A new series of 6-substiuted-4-(2-(4-substituted-benzylidene)hydrazinyl)quinolin-2(1H)-one derivatives have been designed and synthesized. The structure of the synthesized compounds was proved by 1H NMR, 13C NMR, 2D NMR, mass and elemental analyses. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI protocol. Consequently, the most active compounds were further examined against the most sensitive leukemia RPMI-8226 and on healthy cell lines. 6-Chloro-derivative was the most active one; with IC50 = 15.72 ± 1.21 and 46.05 ± 2.36 μM against RPMI-8226 and normal cell lines, respectively. Also, it showed a remarkable inhibitory activity compared to gefitinib on the EGFR TK mutant, wild and on H-RAS in addition to STAT-3 with IC50 = 695.49 ± 21.8, 263.15 ± 15.13, 10.61 ± 0.27 and 1.753 ± 0.81 nM, respectively. Cell cycle analysis of RPMI-8226 cells treated with the 6-chloro-derivative showed cell cycle arrest at G2/M phase (supported by Caspases-3,8, BAX and Bcl-2 studies) with a significant pro-apoptotic activity as indicated by annexin V-FITC staining. Moreover, the docking studies ROCS analysis and Tanimoto scores supported the results. The study illustrated the effect of several factors on compounds activity.
- Abuo-Rahma, Gamal El-Din A.,Aly, Ashraf A.,El-Shaier, Yaseen A. M. M.,Elbastawesy, Mohammed A. I.,Ramadan, Mohamed
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- Design, synthesis, and anticonvulsant evaluation of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives
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The novel group of 4-GABA-3-nitrocoumarines, 1-thiocoumarines, quinolone-2-ones, and their derivatives was designed as potential anticonvulsants using GABA pharmacophore and corresponding heterocyclic moieties. A number of compounds of this group were synthesized and studied in the maximum electroshock seizure (MES) test and in the model of primary-generalized convulsions caused by subcutaneous pentylenetetrazole (scPTZ) in mice. The most active compound in the MES test was found to be 1a (N-(3-nitrocoumarin-4-yl)-4-aminobutyric acid) at a dose range of 60–80 mg/kg that increased the number of survived animals up to 60% in comparison with the control group, whose survival rate was 10%. Compounds 1d (N-(3,6-dinitrocoumarin-4-yl)-4-amino-butyric acid methyl ester) at doses of 10–40 mg/kg and 3a (N-(3-nitro-2-oxo-1,2-dihydroquinolin-4-yl)-4-amino-butyric acid methyl ester) at a dose of 12.5 mg/kg had the most pronounced anticonvulsant effect in scPTZ test. [Figure not available: see fulltext.].
- Mokrov,Litvinova,Voronina,Nerobkova,Kutepova,Kovalev,Gudasheva,Durnev
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p. 1901 - 1911
(2019/08/27)
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- Novel Pyrazoloquinolin-2-ones: Design, synthesis, docking studies, and biological evaluation as antiproliferative EGFR-TK inhibitors
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Two new series of diethyl 2-[2-(substituted-2-oxo-1,2-dihydroquinolin-4-yl)hydrazono]-succinates 6a-g and 1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazoles 7a-f have been designed and synthesized. The structures of the synthesized compounds were proved by IR, mass, NMR (2D) spectra and elemental analyses. The target compounds were evaluated for their in vitro cytotoxic activity against 60 cancer cell lines according to NCI protocol. Consequently, seven compounds were further examined against the most sensitive cell lines, leukemia CCRF-CEM, and MOLT-4. 5-Amino-1-(6-bromo-2-oxo-1,2-dihydroquinolin-4-yl)-1H-pyrazole-3,4-dicarbonitrile (7f) was the most active product, with IC50 = 1.35 uM and 2.42 uM against MOLT-4 and CCRF-CEM, respectively. Also, it showed a remarkable inhibitory activity compared to erlotinib on the EGFR TK with IC50 = 247.14 nM and 208.42 nM, respectively. Cell cycle analysis of MOLT-4 cells treated with 7f showed cell cycle arrest at G2/M phase (supported by Caspases, BAX and Bcl-2 studies) with a significant pro-apoptotic activity as indicated by annexin V-FITC staining. Moreover, the docking study indicated that both the pyrazole moiety and the quinolin-2-one ring showed good fitting into EGFR (PDB code: 1M17). In order to interpret SAR of the designed compounds, and provide a basis for further optimization, molecular docking of the synthesized compounds to known EGFR inhibitors was performed. The study illustrated the effect of several factors on the compounds’ activity.
- Elbastawesy, Mohammed A.I.,Aly, Ashraf A.,Ramadan, Mohamed,Elshaier, Yaseen A.M.M.,Youssif, Bahaa G.M.,Brown, Alan B.,El-Din A Abuo-Rahma, Gamal
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- Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-: C] quinolones as antiproliferative agents
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Pyrano[3,2-c]quinolone structural motifs are commonly found in natural products with diverse biological activities. As part of a research programme aimed at developing the efficient synthesis of natural product-like small molecules, we designed and developed the microwave assisted, facile stereoselective synthesis of two series of carbohydrate fused pyrano[3,2-c]quinolone derivatives (n = 23) starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxyquinolones in shorter reaction times (15-20 min). The antiproliferative activity of these synthesized pyrano[3,2-c]quinolones was determined against MCF-7 (breast) and HepG2 (liver) cancer cells. The selected library members displayed low micromolar (3.53-9.68 μM) and selective antiproliferative activity. These findings on carbohydrate fused pyrano[3,2-c]quinolone derivatives are expected to provide new leads for anticancer drug discovery.
- Kumari, Priti,Narayana, Chintam,Dubey, Shraddha,Gupta, Ashish,Sagar, Ram
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supporting information
p. 2049 - 2059
(2018/03/26)
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- Oxidative Fragmentations and Skeletal Rearrangements of Oxindole Derivatives
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An oxidative sequence for the conversion of oxindoles to structurally distinct heterocyclic scaffolds and aniline derivatives is disclosed by the combination of a copper-catalyzed C-H peroxidation and subsequent base-mediated fragmentation reaction. In contrast to classic enzymatic (i.e., kynurenine pathway) and biomimetic methods (i.e., Witkop-Winterfeldt oxidation) for oxidative indole cleavage, this protocol allows for the incorporation of external nucleophiles. The new transformation displays broad functional group tolerance and is applicable to tryptophan derivatives, opening potential new avenues for postsynthetic modification of polypeptides, bioconjugation, and unnatural amino acid synthesis.
- Klare, Hendrik F. T.,Goldberg, Alexander F. G.,Duquette, Douglas C.,Stoltz, Brian M.
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supporting information
p. 988 - 991
(2017/03/14)
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- Structure of the imine 4-hydroxy-2-quinoline ketone compound, and its preparation and use
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The invention relates to 4-hydroxy-2-quinolinone compounds containing an imine structure, and preparation and an application thereof. A general formula is represented as the formula (I), wherein meanings of groups in the formula are defined in the specification. The compounds represented by the general formula (I) have quite good herbicidal and fungicidal activities and are widely applied in prevention and treatment of weeds and pathogenic bacteria of crops.
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Paragraph 0073; 0076
(2016/10/10)
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- Natural Product-Mimetic Scaffolds with Privileged Heterocyclic Systems: Design, Synthesis, and Evaluation of Antioxidant Activity of Quinazoquinobenzothiazinones
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(Chemical Equation Presented) Structurally diverse quinazolinoquinolinobenzothiazinones based on rutaecarpine structural framework with hybrid structural features of three medicinally privileged heterocyclic systems has been synthesized as natural product-mimetic scaffolds involving the use of multi-step reaction sequences. The synthesized quinazolinoquinolinobenzothiazinones have been evaluated for their antioxidant and radical scavenging activities.
- Sharma, Kshitija,Khandelwal, Sarita,Samarth,Kumar, Mahendra
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p. 220 - 228
(2016/02/10)
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- Synthesis and SAR studies of novel 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives for anticancer activity
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Background and Purpose 4-Phenylquinolin-2(1H)-one (4-PQ) derivatives can induce cancer cell apoptosis. Additional new 4-PQ analogs were investigated as more effective, less toxic antitumour agents. Experimental Approach Forty-five 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives were synthesized. Antiproliferative activities were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliun bromide assay and structure-activity relationship correlations were established. Compounds 9b, 9c, 9e and 11e were also evaluated against the National Cancer Institute-60 human cancer cell line panel. Hoechst 33258 and Annexin V-FITC/PI staining assays were used to detect apoptosis, while inhibition of microtubule polymerization was assayed by fluorescence microscopy. Effects on the cell cycle were assessed by flow cytometry and on apoptosis-related proteins (active caspase-3, -8 and -9, procaspase-3, -8, -9, PARP, Bid, Bcl-xL and Bcl-2) by Western blotting. Key Results Nine 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives (7e, 8e, 9b, 9c, 9e, 10c, 10e, 11c and 11e) displayed high potency against HL-60, Hep3B, H460, and COLO 205 cancer cells (IC50 50 > 50 μM). Particularly, compound 11e exhibited nanomolar potency against COLO 205 cancer cells. Mechanistic studies indicated that compound 11e disrupted microtubule assembly and induced G2/M arrest, polyploidy and apoptosis via the intrinsic and extrinsic signalling pathways. Activation of JNK could play a role in TRAIL-induced COLO 205 apoptosis. Conclusion and Implications New quinolone derivatives were identified as potential pro-apoptotic agents. Compound 11e could be a promising lead compound for future antitumour agent development.
- Chen, Yi-Fong,Lin, Yi-Chien,Morris-Natschke, Susan L.,Wei, Chen-Fang,Shen, Ting-Chen,Lin, Hui-Yi,Hsu, Mei-Hua,Chou, Li-Chen,Zhao, Yu,Kuo, Sheng-Chu,Lee, Kuo-Hsiung,Huang, Li-Jiau
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supporting information
p. 1195 - 1221
(2015/03/04)
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- Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening
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Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2-c]quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP non-competitive CDK5/p25 inhibitors with good CDK2/E selectivity.
- Chatterjee, Arindam,Cutler, Stephen J.,Doerksen, Robert J.,Khan, Ikhlas A.,Williamson, John S.
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p. 6409 - 6421
(2015/01/09)
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- Synthesis of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4-dihydro- 1H-quinolin-2-ones, as novel quinoline derivatives with antibacterial activity
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A novel series of symmetrically substituted 3,3-dibenzyl-4-hydroxy-3,4- dihydro-1H-quinolin-2-ones was synthesized and tested as antimicrobials. The minimum inhibitory concentration (MIC) values of the most active heterocycles were slightly higher than those exhibited by levofloxacin, employed as comparator. Structural factors affecting the activity were explored along three diversification points, including the substituents of the aromatic rings of the 3-benzyl moieties, as well as the functionalization of both, the homocyclic ring of the heterocycle and the quinolonic nitrogen atom. 6-Chloro and 3,3-bis(4′-chlorobenzyl) derivatives showed the lower MIC values. Optimally substituted heterocycles were synthesized, which exhibited enhanced activity.
- Ferretti, Matías D.,Neto, Alexandre T.,Morel, Ademir F.,Kaufman, Teodoro S.,Larghi, Enrique L.
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p. 253 - 266
(2014/06/09)
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- Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one as useful synthon intermediate for synthesis of some new quinolinones
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3-Acetyl-4-methylthioquinolin-2(1H)-one (3) has been prepared and its reactivity towards treatment with different reagents, dilute sulfuric acid, aqueous sodium hydroxide, and hydrogen peroxide, is described. The reactions of compound 3 with benzylamine,
- Hassan, Mohamed M.,Othman, Elham S.,Abass, Mohamed
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p. 1209 - 1225
(2013/06/27)
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- Efficient preparation of 4-hydroxyquinolin-2(1 H)-one derivatives with silver-catalyzed carbon dioxide incorporation and intramolecular rearrangement
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Although 4-hydroxyquinolin-2(1H)-one derivatives have attracted much attention due to their biological benefits, conventional reactions under harsh heat conditions must be employed to provide these key compounds. In the presence of a catalytic amount of s
- Ishida, Tomonobu,Kikuchi, Satoshi,Yamada, Tohru
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p. 3710 - 3713
(2013/08/23)
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- Modified riemschneider reaction of 3-thiocyanatoquinolinediones
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The Riemschneider reaction of 3-thiocyanatoquinoline-2,4(1H,3H)-diones with conc. H2SO4 was investigated. Using different reaction conditions, 13 types of reaction products were isolated. Compounds bearing a Me, Et, or Bu group at C(3) afforded mainly [1,3]thiazolo[5,4-c]quinoline-2,4- diones and 1,9b-dihydro-9b-hydroxythiazolo[5,4-c]quinoline-2,4-diones. In the case of the 3-Bu derivatives of the starting compounds, C-debutylation was also observed. If a Bn group is present at C(3), rapid C-debenzylation of the starting thiocyanates occurred, yielding [1,3]oxathiolo[4,5-c]quinoline-2,4- diones, and mixtures of mono-, di-, and trisulfides derived from 4-hydroxy-3-sulfanylquinoline-2-ones. The reaction mechanism of all of the transformations is discussed. All new compounds were characterized by IR, 1H- and 13C-NMR, and EI and ESI mass spectra, and in some cases, 15N-NMR spectra were also used to characterize new compounds. Copyright
- Rudolf, Ondrej,Mrkvicka, Vladimir,Lycka, Antonin,Rouchal, Michal,Klasek, Antonin
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experimental part
p. 1352 - 1372
(2012/09/25)
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- Synthesis of quinolin-2-one alkaloid derivatives and their inhibitory activities against HIV-1 reverse transcriptase
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Based on an established common pharmacophore of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNTTIs), a series of quinolin-2-one derivatives were synthesized and assayed for their in vitro activities against HIV-1 reverse transcriptase (RT) for the first time. Some of the tested compounds were active against HIV-1 RT. Compounds 4a2 and 4d2 showed inhibitory activities with IC50 values of 0.21 and 0.15 μM, respectively, with a mode of interaction with RT residues of the allosteric pocket similar to that of efavirenz.
- Cheng, Pi,Gu, Qiong,Liu, Wei,Zou, Jian-Feng,Ou, Yang-Yong,Luo, Zhong-Yong,Zeng, Jian-Guo
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experimental part
p. 7649 - 7661
(2011/11/05)
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- Characterization of 4-methyl-2-oxo-1,2-dihydroquinolin-6-yl acetate as an effective antiplatelet agent
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We have studied earlier a membrane bound novel enzyme Acetoxy Drug: protein transacetylase identified as Calreticulin Transacetylase (CRTAase) that catalyzes the transfer of acetyl groups from polyphenolic acetates (PAs) to the receptor proteins and thus modulating their biological activities. In this communication, we have reported for the first time that acetoxy quinolones are endowed with antiplatelet action by virtue of causing CRTAase catalyzed activation of platelet Nitric Oxide Synthase (NOS) by way of acetylation leading to the inhibition of ADP/Arachidonic acid (AA)-dependent platelet aggregation. The correlation of specificity of platelet CRTAase to various analogues of acetoxy quinolones with intracellular NO and consequent effect on inhibition of platelet aggregation was considered crucial. Among acetoxy quinolones screened, 6-AQ (4-methyl-2-oxo-1,2-dihydroquinolin-6-yl acetate/6-acetoxyquinolin-2-one, 22) was found to be the superior substrate to platelet CRTAase and emerged as the most active entity to produce antiplatelet action both in vitro and in vivo. 6-AQ caused the inhibition of cyclooxygenase-1 (Cox-1) resulting in the down regulation of thromboxane A2 (TxA2) and the inhibition of platelet aggregation. Structural modification of acetoxy quinolones positively correlated with enhancement of intracellular NO and antiplatelet action.
- Priya, Nivedita,Gupta, Anjali,Chand, Karam,Singh, Prabhjot,Kathuria, Abha,Raj, Hanumantharao G.,Parmar, Virinder S.,Sharma, Sunil K.
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experimental part
p. 4085 - 4094
(2010/08/06)
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- Clean and convenient one-pot synthesis of 4-hydroxycoumarin and 4-hydroxy-2-quinolinone derivatives
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A simple, efficient, and environmentally friendly procedure has been developed for the reaction of Meldrum's acid with phenol, substituted phenols, aniline, or substituted anilines with Eaton's reagent (phosphoric anhydride+methylsulfonic acid) as cyclization reagent. 4-Hydroxycoumarins and 4-hydroxy-2-quinolinones were synthesized in moderate yields by carrying out the reaction in solvent-free, convenient, and clean one-pot preparation.
- Gao, Wen-Tao,Hou, Wen-Duan,Zheng, Mei-Ru,Tang, Li-Jun
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experimental part
p. 732 - 738
(2011/03/17)
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- The laccase-catalyzed domino reaction between catechols and heterocyclic 1,3-dicarbonyls and theunambiguous structure elucidation of the products by NMR spectroscopy and X-ray crystal structure analysis
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(Chemical Equation Presented) The laccase-catalyzed reaction between catechols and heterocyclic 1,3-dicarbonyls (pyridinones, quinolinones, thiocoumarins) using aerial oxygen as the oxidant delivers benzofuropyridinones, benzofuroquinolinones, and thiocou
- Hajdok, Szilvia,Conrad, Juergen,Leutbecher, Heiko,Strobel, Sabine,Schleid, Thomas,Beifuss, Uwe
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body text
p. 7230 - 7237
(2010/01/16)
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- Synthesis of 4-hydroxy-3-formylideneamino-lH/methyl/phenylquinolin-2-ones
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An efficient method for the synthesis of 4-hydroxy-3-formylideneamino-l H/methyl/phenylquinolin-2-ones by the condensation of corresponding 4-hydroxy-3-formyl-l///methyl/phenylquinolin-2-one with substituted anilines/aliphatic primary amines is reported. The carboxaldehyde in turn is prepared starting either from substituted anilines or benzoic acid. The structures of compounds are established by the elemental analysis and spectral data.
- Bhudevi,Ramana,Mudiraj, Anwita,Reddy
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experimental part
p. 255 - 260
(2009/12/03)
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- Structure-activity relationships of heteroaromatic esters as human rhinovirus 3C protease inhibitors
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Human rhinovirus 3C protease (HRV 3Cpro) is known to be a promising target for development of therapeutic agents against the common cold because of the importance of the protease in viral replication as well as its expression in a large number of serotypes. To explore non-peptidic inhibitors of HRV 3Cpro, a series of novel heteroaromatic esters was synthesized and evaluated for inhibitory activity against HRV 3Cpro, to determine the structure-activity relationships. The most potent inhibitor, 7, with a 5-bromopyridinyl group, had an IC50 value of 80 nM. In addition, the binding mode of a novel analog, 19, with the 4-hydroxyquinolinone moiety, was explored by molecular docking, suggesting a new interaction in the S1 pocket.
- Im, Isak,Lee, Eui Seung,Choi, Soo Jeong,Lee, Ju-Yeon,Kim, Yong-Chul
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scheme or table
p. 3632 - 3636
(2010/03/24)
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- Synthesis of zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives
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Zwitterionic 4-hydroxy-2(1H)-quinolinone derivatives were synthesized through a unique reaction of 4-hydroxy-2(1H)-quinolinone with p-benzoquinone and N-heterocyclic aromatics. The zwitterions possessed astropisomeric nature. A possible mechanism of the reaction was presented.
- Zhang, Sheng-Ling,Huang, Zhi-Shu,Li, Yue-Ming,Chan, Albert S.C.,Gu, Lian-Quan
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p. 4403 - 4407
(2008/09/20)
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- Microwave prompted multigram synthesis, structural determination, and photo-antiproliferative activity of fluorinated 4-hydroxyquinolinones
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3-Unsubstituted 4-hydroxyquinolin-2(1H)-one containing F and CF3 substituent in ring is important pharmacological and synthetic target and basic synthones for a number of antibacterial fluoroquinolones and is promising potent and selective glycine site NMDA receptors. A simple facile one-step microwave enhanced multigram synthesis of such fluorinated quinolones in reasonable purity has been developed in excellent yield (85-94%) in 3-5 min, whereas conventional synthesis required the harsh conditions, long reaction period with use of environmentally unacceptable regents giving the required product in lower yield. The phototoxicity as well as the cytotoxic activities of the title compounds are evaluated against leukemia- and adenocarcinoma-derived cell lines in comparison to the normal human keratinocytes. Structure-activity relationships between the chemical structures and the antimycobacterial, antifungal activity of the evaluated compounds are also discussed.
- Arya, Kapil,Agarwal, Manish
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- Enzymatic formation of quinolone alkaloids by a plant type III polyketide synthase
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(Chemical Equation Presented) Benzalacetone synthase from Rheum palmatum efficiently catalyzed condensation of N-methylanthraniloyl-CoA (or anthraniloyl-CoA) with malonyl-CoA (or methylmalonyl-CoA) to produce 4-hydroxy-2(1H)-quinolones, a novel alkaloidal scaffold produced by a type III polyketide synthase (PKS). Manipulation of the functionally divergent type III PKSs by a nonphysiological substrate thus provides an efficient method for production of pharmaceutically important quinolone alkaloids.
- Abe, Ikuro,Abe, Tsuyoshi,Wanibuchi, Kiyofumi,Noguchi, Hiroshi
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p. 6063 - 6065
(2008/02/07)
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- A convenient one-pot synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2(1H)-one
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An improved one-pot synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2(1H)-one from 2-hydroxyacetophenone, 2-mercaptoacetophenone, and 2-aminoacetophenone, respectively, is described. The synthetic strategies involve the acylation and internal ring cyclization. This method is readily amenable to large-scale synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2(1H)-one derivatives in high yields.
- Jung,Jung,Park
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p. 1195 - 1200
(2007/10/03)
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- Quinone methide reactions: Synthesis of novel pyranodiquinolines
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The reaction of alkaline 4-hydroxyquinolin-2(1H)-ones (1) with vinyl acetate has been studied.Interestingly, 1,1-diquonolinoethane formed via a quinoline-quinone methide intermediate undergoes dehydration in situ by two paths yielding the isomeric 7-methylpyranodiquinolines (3 and 4).
- Balasubramanian, C.,Kumaraswami, K.,Dharmaraj, N.,Mohan, P. S.
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p. 460 - 462
(2007/10/02)
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- Quinoline Alkaloids. Synthesis of Khaplofoline, Ribalinine, and Flindersine
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Reaction of 4-hydroxy-3-prenylquinolin-2(1H)one (5a) with iodine and silver acetate gave a iodopyranoquinoline (6a), which was then converted into the alkaloids khaplofoline (1) and ribalinine (2).Reaction of 5a with iodine and mercuric oxide afforded a mixture of 6a and its angular isomer 7a; the conversion of latter into flindersine (10) is described.Keywords: Pyranoquinoline Alkaloids, Khaplofoline, Ribalinine, Flindersine
- Subramanian, M.,Mohan, P. S.,Shanmugam, P.,Prasad, K. J. Rajendra
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p. 1016 - 1020
(2007/10/02)
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- A CONVENIENT APPROACH TO THE SYNTHESIS OF PRENYL-, FURO- AND PYRANO-QUINOLINE ALKALOIDS OF THE RUTACEAE
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A convenient method for the synthesis of 4-hydroxy-3-prenyl-2-quinolones, wjich have been recognised as precursors to prenyl-, furo- and pyranoquinoline alkaloids of the Rutaceae is described.The methodology involves C,C-diprenylation of 2,4-dihydroxyquinoline followed by partial deallylation using sodium hydrogen telluride reagent.
- Shobana, N.,Yeshoda, P.,Shanmugam, P.
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p. 757 - 762
(2007/10/02)
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- MUSHROOM TYROSINASE CATALYSED SYNTHESIS OF COUMENTANS, BENZOFURAN DERIVATIVES AND RELATED HETEROCYCLIC COMPOUNDS
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Full details of an improved synthesis of coumestan derivatives and their structural analogues, viz., wedelolactone, 11-hydroxy aureol, 11-hydroxy coumestrol along benzofuran derivatives and related heterocyclic systems are reported by coupling of in situ generated o-quinones from catechols catalysed by mushroom tyrosinase with various reatants.
- Pandey, G.,Muralikrishna, C.,Bhalerao, U. T.
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p. 6867 - 6874
(2007/10/02)
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- Sodium Hydrogen Telluride- An Efficient Reagent for Deblocking of Aryl Ethyl Carbonates
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Sodium hydrogen telluride is found to be a mild and efficient reagent for deblocking of aryl ethyl carbonates.
- Shobana, N.,Amirthavalli, M.,Deepa, V.,Shanmugam, P.
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p. 965 - 966
(2007/10/02)
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- Synthesis of Substituted N-Hydroxylactams, Lactams, Quinoline-N-oxides, and Quinolines by Catalyzed Reductive Cyclization of 2-Nitrocinnamoyl Derivatives with Hydrogen/Platinum Black
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Substituted nitrobenzenes 1a-1m, consisting of two series of 6 analogous compounds, containing the structural unit of an α,β-substituted 2-nitrocinnamoyl group have been reductively cyclized by means of hydrogen in the presence of platinum black catalyst to form four types of heterocycles: N-hydroxylactams 2a and b, lactams 3 and 4, quinoline-N-oxides 5a-d, and quinolines 6a and b.The type of substituents at the 2-nitrocinnamoyl group is of significance for the type of heterocycle formed in this reaction.It is of special interest that by the use of the reduction system hydrogen/platinum black the probability to obtain N-hydroxylactams or quinoline-N-oxides, which are difficult to obtain by alternative procedures, becomes much higher than by the use of many reducing agents noncatalytically.
- Sicker, D.,Rabe, A.,Zakrzewski, A.,Mann, G.
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p. 1063 - 1070
(2007/10/02)
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- Sodium Hydrogen Telluride - A New Convenient Reagent for Deblocking Allyl Carboxylates and Allyl Phenyl Ethers
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Sodium hydrogen telluride is found to be a mild and effective reagent for cleaving allyl carboxylates as well as allyl phenyl ethers.
- Shobana, N.,Shanmugam, P.
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- Ylides of Heterocycles, VIII. Reactions of Iodonium-Ylides with Acids
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The reaction of various organic and inorganic acids (HX) with iodonium ylides 2 leads to nucleophilic substitution of the iodobenzene substituent by the anion X(-) to yield the heterocycles 5.Some of them are hydrolyzed to the hydroxy compounds 3 or reduced to the starting compounds 1 under the reaction conditions.Reaction of the iodonium ylide 2b with monomethyl sulfate gives the salt 9, which with bases undergoes nucleophilic substitution to compounds 8 and 10-12, respectively, or is converted to 2b again. - Keywords: 3-Acetoxy-4-hydroxy-2-quinolones; 2-Oxoquinoline-4-olates; 3-Substituted 4-hydroxy-2-quinolones
- Pongratz, Erik,Kappe, Thomas
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p. 231 - 242
(2007/10/02)
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