- Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase
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A series of 3-amino-6,7-dimethoxycoumarins conjugated with the N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluo-robenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value of 1.53 ± 0.01 nM. Docking studies revealed that the synthesized compounds inhibit the target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme.
- Khunnawutmanotham, Nisachon,Laongthipparos, Cherdchai,Saparpakorn, Patchreenart,Chimnoi, Nitirat,Techasakul, Supanna
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- Synthesis of substituted 3-aminocoumarins from ethyl N-2- hydroxyarylideneglycinates
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3-Aminocoumarin and its derivatives are prepared by a thermal (150- 170°C) conversion reaction on the corresponding ethyl N-2- hydroxyarylideneglycinates,[2-HOC6H3(X)CH=NCH2CO2C2Hs; X = H, 5-Br, 5- OH, 5-NO2, 3-OMe, 4-OMe, and 5,6-benzo], which are synthesized by condensing ethyl glycinate hydrochloride with substituted salicylaldehyde.
- Khoo, Lian Ee
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- Tyrosine-like condensed derivatives as tyrosinase inhibitors
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Objectives We report the pharmacological evaluation of a new series of 3-aminocoumarins differently substituted with hydroxyl groups, which have been synthesized because they include in their structures the tyrosine fragment (tyrosine-like compounds), with the aim of discovering structural features necessary for tyrosinase inhibitory activity. Methods The synthesized compounds 4 and 7-9 were evaluated in vitro as mushroom tyrosinase inhibitors. Key findings Two of the described compounds showed lower IC50 (concentration giving 50% inhibition of tyrosinase activity) than umbelliferone, used as a reference compound. Conclusions Compound 7 (IC50 = 53 μm) was the best tyrosinase inhibitor of this small series, having an IC50 value 10-fold lower than umbelliferone. Compound 7 (3-amino-7-hydroxycoumarin) had amino and hydroxyl groups precisely mimicking the same positions that both groups occupy on the tyrosine molecule. 2012 The Authors. JPP
- Matos, Maria Joao,Santana, Lourdes,Uriarte, Eugenio,Serra, Silvia,Corda, Marcella,Fadda, Maria Benedetta,Era, Benedetta,Fais, Antonella
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- Design, synthesis and biological evaluation of selective hybrid coumarin-thiazolidinedione aldose reductase-II inhibitors as potential antidiabetics
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Thiazolidinediones (TZD), benzopyrans are the proven scaffolds for inhibiting Aldose reductase (ALR2) activity and their structural confluence with the retention of necessary fragments helped in designing a series of hybrid compounds 2-(5-cycloalkylidene-2,4-dioxothiazolidin-3-yl)-N-(2-oxo-2H-chromen-3-yl)acetamide (10a-n) for better ALR2 inhibition. The compounds were synthesized by treating substituted 3-(N-bromoacetyl amino)coumarins (9a-d) with potassium salt of 5-cyclo alkylidene-1,3-thiazolidine-2,4-diones (4a-d). The inhibition activity against ALR2 with IC50 values range from 0.012 ± 0.001 to 0.056 ± 0.007 μM. N-[(6-Bromo-3-coumarinyl)-2-(5-cyclopentylidene-2,4-dioxothiazolidin-3-yl)] acetamide (10c) with cyclopentylidene group on one end and the 6-bromo group on the other end showed better inhibitory property (IC50 = 0.012 μM) and selectivity index (324.166) against the ALR2, a forty fold superiority over sorbinil, a better molecule over epalrestat and rest of the analogues exhibited a far superior response over sorbinil and slightly better as compared with epalrestat. It was further confirmed by the insilico studies that compound 10c showed best inhibition activity among the synthesized compounds with a high selectivity index against the ALR2. In invivo experiments, supplementation of compound 10c to STZ induced rats delayed the progression of cataract in a dose-dependent manner warranting its further development as a potential agent to treat the diabetic secondary complications especially cataract.
- Basude, Manohar,Gudipudi, Gopinath,Gundla, Rambabu,Kumar Pasala, Vijay,Nareshkumar, Devasani,Sankeshi, Venu,Srinivas, Burra,Yadaiah Goud, E.,singh Jadav, Surendar
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- An efficient and facile synthesis of substituted 3-aminocoumarins under mw irradiation in dry media
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A variety of 3-aminocoumarins were prepared by reaction of salicylaldehyde derivatives with benzoylglycine catalyzed by piperidine under microwave irradiation (MWI) and subsequent acid hydrolysis. The structure of products was proven by elemental analysis, IR, NMR and Mass spectra. These investigations will contribute to development of environmentally friendly and inexpensive processes in organic synthesis.
- Valizadeh, Hassan,Shockravi, Abbas
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- A highly selective fluorescent probe for detection of Cd2+ and HSO3- based on photochromic diarylethene with a triazole-bridged coumarin-quinoline group
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A novel photochromic diarylethene containing a quinoline-linked 3-aminocoumarin Schiff base unit (1O) was synthesized and used for the selective detection of Cd2+ and HSO3-. The synthesized probe exhibited a straightforward response for the selective detection of Cd2+. Its fluorescence emission red-shifted ~126 nm and was enhanced 24.9 fold in the presence of Cd2+. Meanwhile, the fluorescence color of 1O changed from dark cyan to golden yellow. The binding stoichiometry between 1O and Cd2+ was determined to be 1:1. A molecular logic circuit with three inputs and one output was successfully constructed with its light and metal-responsive behaviors. In addition, 1O was able to selectively recognize HSO3- with a 135-fold enhanced fluorescence emission and a notable fluorescence color change from dark cyan to bright cyan. The 1H NMR and mass spectrometry analyses suggest that the HSO3- sensing of 1O is based on the hydrolysis of the Schiff base group of 1O.
- Guo, Shuli,Liu, Gang,Fan, Congbin,Pu, Shouzhi
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- Design and synthesis of aminocoumarin derivatives as DPP-IV inhibitors and anticancer agents
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DPP-IV “a moonlighting protein” has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 μM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay. One of the compounds has shown very good anticancer activity with IC50 value 24 ± 0.1 nM against A549 cell line.
- Soni, Rina,Soman, Shubhangi S.
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- Development of surface immobilized 3-azidocoumarin-based fluorogenic probe via strain promoted click chemistry
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A new class of imaging probe, a fluorogenic version of 1, 3-dipolar cycloaddition of azides and alkynes has been developed. 3-azidocoumarin scaffolds were selectively immobilized on the DBCO modified bead surface via SPAAC and provide direct and strong fluorescence in fluorescence microscopy. This developed click-on beads could be applied to label various biomolecules, such as nucleic acids, proteins and other molecules. To this end, 5′(7-hydroxy 3-azido coumarin) labelled DNA primer also displayed strong fluorescence upon successful immobilization on the bead surface.
- Bharathi, M. Vijaya,Chhabra, Mohit,Paira, Priyankar
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- Design, synthesis and biological evaluation of amino organophosphorus imidazoles as a new type of potential antimicrobial agents
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A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents. Bioactive evaluation in vitro showed that compound 3f exhibited equipotent or superior anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) and anti-S. cerevisiae efficiencies (minimal inhibitory concentration (MIC)=2 μg/mL) to clinical drugs, and the combinations with antibacterial or antifungal drugs enhanced the antimicrobial efficiency. Highly active molecule 3f showed low propensity for bacteria to develop resistance, and the preliminary action mechanism studies demonstrated that 3f was membrane-active, but had no significant intercalation towards MRSA DNA. The computational study on 3f reasonably explained its high antimicrobial activity. Experimental data revealed that ground-state 3f-HSA complexes were formed mainly through hydrophobic interactions and hydrogen bonds with a spontaneous process, and the non-radioactive energy transfer from HSA to 3f occurred beyond F?rster resonance energy transfer theory. The participation of metal ions in 3f-HSA supramolucular system could increase the concentration of free compound 3f, and shorten its storage time and half-life in the blood to improve the maximum antimicrobial efficacy.
- Gao, Wei-Wei,Rasheed, Syed,Tangadanchu, VijaiKumarReddy,Sun, Yi,Peng, Xin-Mei,Cheng, Yu,Zhang, Feng-Xiu,Lin, Jian-Mei,Zhou, Cheng-He
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- Synthesis and cytotoxicity study of novel 3-(triazolyl)coumarins based fluorescent scaffolds
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Recently a choice of fluorescent bioimaging probes have been developed as medical diagnostic tools. Herein, we have introduced a series of coumarin-based target specific probes for cancer theranostic application which play a dual role in the field of both diagnosis and therapy. A fluorogenic version of 1,3-dipolar cycloaddition between azides and alkynes (DBCO) has been introduced to develop the triazolylcoumarin based fluorescent scaffolds. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human epitheloid cervix carcinoma (HeLa) cell line. It was established that triazolylcoumarins (5c and 5d) are having electronegative substitution in the benzene ring displayed most effective anticancer profile in both the cell lines. Compounds 5a and 5d exhibited maximum quantum yield and strong cellular uptake in the MCF-7 cell line.
- Sinha, Sohini,Kumaran, Anuja Plavuvalapil,Mishra, Debasish,Paira, Priyankar
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- A novel class of human 15-LOX-1 inhibitors based on 3-hydroxycoumarin
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Inflammations, sensitivities, and some cancers in mammals are intimately linked to the activity of lipo-oxygenase enzymes. Owing to the importance of these enzymes, mechanistic studies, product analysis, and synthesis of inhibitors have expanded. In this study, a series of hydroxycoumarins, methoxy-3-hydroxy coumarins, and 7-alkoxy-3-hydroxy coumarins were synthesized and evaluated as potential inhibitors of human 15-LOX-1. Among the synthetic coumarins, 7-methoxy-3-hydroxycoumarin derivative demonstrated potent inhibitory activity and the compound, 5f, showed the best result. Radical scavenging assessment, IC50, HNMR, and DPPH bleaching results indicate that the electronic properties are the major factors for the lipo-oxygenase inhibition potency of the synthetic coumarins. Based on the theoretical studies, it was suggested that the mesomeric effect of the substituent at the seventh position of the benzene ring is one of the major factors in the stability of the oxy-radical intermediate.
- Alavi, Seyed Jamal,Sadeghian, Hamid,Seyedi, Seyed Mohammad,Salimi, Alireza,Eshghi, Hossein
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- Synthesis, CYP 450 evaluation, and docking simulation of novel 4-aminopyridine and coumarin derivatives
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Four series of novel compounds based on 4-aminopyridine, glatiramer acetate, pyrone, and coumarin backbones were sufficiently synthesized and identified by spectroscopic methods. CYP enzyme inhibition assays of five predominate human P450 isozymes indicate that all compounds, except for 4-hydrazide pyridine 1c, seem to be less toxic than 4-aminopyridine. Further investigation of the compounds using molecular docking experiments revealed different, the same, or stronger binding modes for most of the synthesized compounds, with both polar and hydrophobic interactions with the 1WDA and 1J95 receptors compared to benzoyl l-arginine amide and 4-aminopyridine, respectively. These results introduce the synthesized compounds as K+ channel blockers that could be considered for in vivo CNS disease studies.
- Ghalehshahi, Hajar G.,Balalaie, Saeed,Sohbati, Hamid R.,Azizian, Homa,Alavijeh, Mohammad S.
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- Synthesis of new 2H,4H-benzopyrano[3,4-b]pyridine-1,3,5-trione derivatives via carbon suboxide
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The new 2H,4H-[1]benzopyrano[3,4-b]pyridine-1,3,5-trione derivatives 10a-f were prepared in the following three steps; the first preparation of new N-(tert-butoxycarbonyl)-3-amino-2H-1-benzopyran-2-one derivatives 5a-f by reaction of coumarin-3-carboxylic acids and diphenylphosphorlyazide, then hydrolysis of 5a-f with gaseous hydrogen chloride to give the corresponding amines 7a-f, and finally the preparation of 10a-f by reaction of 7a-f and carbon suboxide in the presence of a Lewis acid.
- Bonsignore, Leonardo,Loy, Giuseppe
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- Hydrolysis-free synthesis of 3-aminocoumarins
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A commonly encountered problem in the synthesis of 3-aminocoumarins is the formation of 3-hydroxycoumarins. A solution to this problem, which involves non-aqueous formation of the 3-aminocoumarin system, is described.
- Kudale, Amit A.,Kendall, Jamie,Warford, C. Chad,Wilkins, Natasha D.,Bodwell, Graham J.
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- Mild and highly efficient deacetylation of acetamido and acetoxy coumarins: A convenient and expeditious synthesis of substituted 3-aminocoumarins
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A convenient protocol for efficient and cost-effective method for synthesis of substituted 3-aminocoumarins has been developed. The synthetic route involves expeditious and fast quantitative deacetylation of readily available acetamido derivative under anhydrous acidic conditions, employing thionyl chloride in methanol, without formation of undesired substituted 3-hydroxycoumarins. The method is suitable for derivatives bearing electron-donating as well as electron-withdrawing groups at position 7 of the coumarin scaffold. Under these conditions, a series of acetoxy substituted 3-dialkylaminocoumarins has been also successfully deacetylated to afford easily isolable corresponding hydroxy derivatives in high yields.
- Krajňáková, Jana,Joniak, Jakub,Putala, Martin,Górová, Renáta,Jurdáková, Helena,Stankovi?ová, Henrieta
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supporting information
p. 3277 - 3291
(2021/09/02)
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- Design and synthesis of benzyl aminocoumarin and its anti-Alzheimer's activity
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Benzylaminocoumarin is a kind of compound with coumarin skeleton and benzylamino side chain structure at positions 3 and 4. Our group has previously explored the AD activity of 3-(4-aminophenyl) coumarin and obtained benzylaminocoumarin by further structural modification of benzamide side chains. A total of 29 benzylaminocoumarins were synthesized, and the compounds were tested for anti-AD-related activities, and compoundsM3,M11,M21andM26were found to show good AChE inhibitory activity byin vitroactivity experiments, with compoundM11(IC50= 0.068 ± 0.04) showing better AChE inhibitory activity than the positive drug donepezil (IC50= 0.079 ± 0.008). The compound showed good MAO inhibitory activity againstM3andM11, of which compoundM11(IC50= 6.312 ± 0.03) showed the best MAO-B inhibitory activity, but was weaker than the positive drug donepezil (IC50= 1.697 ± 0.01). The experimental results showed that compoundsM21andM26could selectively inhibit the AChE activity, and their probability of producing toxic side effects was low. CompoundM11shows dual AChE and MAO inhibitory activity and can be used as a potential therapeutic agent for the treatment of AD. In anti-AD multitarget drug research, multitarget inhibitors have low limitations and are able to produce better therapeutic effects on the entire disease system.
- Hao, Canhua,Miao, Yuhang,Pan, Yinbo,Sun, Jie,Sun, Xiaoya,Wang, Xiaojing,Yun, Yinling,Zhang, Qiang
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p. 17287 - 17300
(2021/10/06)
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- Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity
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A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe3+ values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-β1-42 (Aβ1-42) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.
- Bai, Renren,Gu, Jinping,Guo, Jianan,Jiang, Xiaoying,Lv, Yangjing,Mi, Zhisheng,Shi, Yuan,Xie, Yuanyuan,Yao, Chuansheng,Zhang, Changjun,Zhou, Tao
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- Coumarin hybrid pyridinone amide derivative with potential anti-AD activity and preparation method and application of derivative
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The invention discloses a coumarin hybrid pyridinone amide derivative and a preparation method and application thereof. The coumarin hybrid pyridinone amide derivative and pharmacologically acceptablesalt thereof are shown in the formula (I) and the formula (II), and the derivative can be used for preparing drugs for resisting the Alzheimer's disease, the Parkinson's disease or treating other diseases or symptoms by suppressing monoamine oxidase, chelating metallic iron ions, resisting A and resisting oxidation.
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Paragraph 0438; 0442; 0443
(2020/02/27)
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- Synthesis, antimicrobial and chitinase inhibitory activities of 3-amidocoumarins
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A series of 3-amidocoumarins has been synthesized and tested in vitro for their anitimicrobial and chitinase inhibitory activities. Among these, compounds 5k, 5l, 8b–8d, 8f and 8g exhibited good antibacterial activity with MIC values in the range of 6.25–25 μg/mL against some of the tested strains while compounds 5l, 8b, 8c and 8f showed good activity against at least one or two fungal strains. Some of the assayed compounds 5d, 5k, 5l, 8b and 8c displayed significant chitinase inhibitory activity with IC50 values in the range of 3.74–5.6 μM. Among them, 5l proved to be potent chitinase inhibitor with IC50 value of 3.74 μM. To better understand the enzyme-inhibitor interactions molecular docking study of all the synthesized compounds was carried out on Aspergillus fumigatus chitinase 1W9U. The compound 5l showed high binding affinity with the receptor with binding energy value of ?8.44 Kcal/mol. This study also provides structure activity relationship (SAR) of synthesized compounds.
- Butcher, R. J.,Katiyar, Diksha,Sharma, Rajesh Kumar,Singh, Vineeta,Tiwari, Neha
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- Evaluation of novel coumarin-proline sulfonamide hybrids as anticancer and antidiabetic agents
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Cancer and diabetes are considered as two major diseases affecting human health worldwide. Various therapies are available for treatment of cancer and diabetes individually, peptide linkage containing proline sulfonamide can be a promising therapy for treatment of both cancer as well as diabetes. Here, we report design and synthesis of novel coumarin-proline sulfonamide derivatives as anticancer and antidiabetic agents. All the synthesized compounds were screened for their anticancer activity against lungs cancer cell line (A549) and breast cancer cell line (MCF7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye (MTT)assay and antidiabetic activity using DPP-IV inhibition assay. Compound 16b showed excellent activity against breast cancer cell line (MCF7) with IC50 value of 1.07 μM. All compounds showed moderate DPP-IV inhibition.
- Durgapal, Sunil Dutt,Soman, Shubhangi S.
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supporting information
p. 2869 - 2883
(2019/08/22)
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- A natural product inspired fragment-based approach towards the development of novel anti-bacterial agents
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The discovery of new antibiotics with novel modes of action to combat antimicrobial resistance (AMR) is of vital importance. The natural product simocyclinone D8 (SD8) is a potent inhibitor of DNA gyrase. Its bi-functional structure and novel mode of action serve as an inspiring lead for antibiotic development. Herein we describe a proof of principle fragment-based approach towards the development of a new class of coumarin-quinolone hybrids. We demonstrate that the coumarin moiety is required for the observed inhibitory activity (IC50 ~ 3 μM) of the hybrid compound, which is in part mediated through stabilisation of a cleaved-DNA intermediate.
- Austin, Michael J.,Hearnshaw, Stephen J.,Mitchenall, Lesley A.,McDermott, Paul J.,Howell, Lesley A.,Maxwell, Anthony,Searcey, Mark
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supporting information
p. 1387 - 1391
(2016/07/21)
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- Efficient Synthesis of Functionalized Pyrido[2,3- c ]coumarin Derivatives by a One-Pot Three-Component Reaction
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A methanesulfonic acid promoted three-component reaction has been developed for the synthesis of functionalized pyrido[2,3-c]coumarin derivatives from ketones, aromatic aldehydes, and 3-aminocoumarin. In this simple and efficient protocol, products were obtained in moderate to good yields (28 examples). The reaction proceeds by an asynchronous [4+2] cycloaddition (inverse-electron-demand Diels-Alder reaction).
- Chen, Zhiwei,Hu, Lele,Peng, Fei
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p. 1888 - 1892
(2016/07/16)
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- Oxydehydrogenative aromatization of fused 3-aminopyran-2-ones on carbon surfaces: A simple approach towards 3-amino-5-hydroxycoumarin derivatives
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Aromatization of selected 3-acylamino-5,6,7,8-tetrahydro-2H-1-benzopyran-2, 5-diones, yielding the corresponding 3-acylamino-5-hydroxycoumarins, was achieved by dehydrogenation with molecular oxygen in the presence of activated carbon. The use of nonpolar solvents and high temperatures was crucial for attaining satisfactory conversions. The 3-benzoylamino-5,6,7,8- tetrahydrocoumarin without a 5-keto group and the 8-oxo analogue as well as the 5-oxo-5,6,7,8-tetrahydrocoumarins containing a free 3-amino group were less efficiently aromatized.
- Stefane, Bogdan,Pozgan, Franc
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p. 1329 - 1335
(2014/07/22)
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- Synthesis of 3-aminochromenes: The Zincke reaction revisited
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3-Aminocoumarines and 2-iminochromen-3-amines were efficiently prepared from the Zincke-ring-opening reaction of the corresponding 2H-chromen-3- pyridinium chlorides using N-methylpiperazine. This methodology unravels the marked potential of pyridinium salts as protective groups for primary amines. These scaffolds can be considered important building blocks for new novobiocin analogues and heterocyclic compounds.
- Costa, Marta,Rodrigues, Ana I.,Proen?a, Fernanda
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p. 4869 - 4875
(2014/07/07)
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- Antimicrobial and antioxidant activities of new metal complexes derived from 3-aminocoumarin
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3-Aminocoumarin (L) has been synthesized and used as a ligand for the formation of Cr(III), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different spectroscopic methods. The elemental analyses revealed that the complexes where M=Ni(II) and Cu(II) have the general formulae [ML2Cl2], while the Cr(III) complex has the formula [CrL2Cl2]Cl. The molar conductance data reveal that all the metal chelates, except the Cr(III) one, are non-electrolytes. From the magnetic and UV-Visible spectra, it is found that these complexes have octahedral structures. The stability for the prepared complexes was studied theoretically using Density Function Theory. The total energy for the complexes was calculated and it was shown that the copper complex is the most stable one. Complexes were tested against selected types of microbial organisms and showed significant activities. The free radical scavenging activity of metal complexes have been determined by measuring their interaction with the stable free radical DPPH and all the compounds have shown encouraging antioxidant activities.
- Kadhum, Abdul Amir H.,Mohamad, Abu Bakar,Al-Amiery, Ahmed A.,Takriff, Mohd S.
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experimental part
p. 6969 - 6984
(2011/10/11)
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- Generation of profluorescent isoindoline nitroxides using click chemistry
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Novel profluorescent nitroxides bearing a triazole linker between the coumarin fluorophore and an isoindoline nitroxide were prepared in good yields using the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction (CuAAC). Nitroxides containing 7-hydroxy and 7-diethylamino substitution on their coumarin rings displayed significant fluorescence suppression, and upon reaction with methyl radicals, normal fluorescence emission was returned. The fluorescence emission for the 7-hydroxycoumarin nitroxide and its diamagnetic analogue was found to be strongly influenced by pH with maximal fluorescence emission achieved in basic solution. Solvent polarity was also shown to affect fluorescence emission. The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic analogues makes these compounds ideal tools for monitoring processes involving free-radical species.
- Morris, Jason C.,McMurtrie, John C.,Bottle, Steven E.,Fairfull-Smith, Kathryn E.
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scheme or table
p. 4964 - 4972
(2011/08/05)
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- Novel synthesis and cytotoxic activity of some chromeno[3,4-b]pyrrol-4(3H)- ones
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1-Methylchromeno[3,4-b]pyrrol-4(3H)-one and 1-phenylchromeno[3,4-b]pyrrol- 4(3H)-one derivatives have been synthesized by cyclization of amides obtained by condensing α-halo ketones with 3-amino-chromenones, which show cytotoxic activity against lung, colon, and breast cancer cell lines.
- Soman,Thaker,Rajput
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scheme or table
p. 1514 - 1519
(2012/01/05)
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- Simple and efficient copper(I)-catalyzed access to three versatile aminocoumarin-based scaffolds using isocyanoacetate
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An efficient method has been developed for the one-pot copper(I)-catalyzed synthesis of 3-aminocoumarin and its derivatives, such as 3-substituted methylideneaminocoumarins and chromeno[3,4-d]imidazol-4(1H)-ones. Significantly, the strategy presents a straightforward and efficient approach to constructing biologically useful molecular scaffolds.
- Meng, Tao,Zou, Yiquan,Khorev, Oleg,Jin, Yu,Zhou, Huayong,Zhang, Yongliang,Hu, Dingyu,Ma, Lanping,Wang, Xin,Shen, Jingkang
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supporting information; experimental part
p. 918 - 924
(2011/06/21)
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- An expeditious copper-catalyzed access to 3-aminoquinolinones, 3-aminocoumarins and anilines using sodium azide
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An efficient copper-catalyzedin in situ C-(sp2)-NH2 bond formation to provide a range of 3-aminoquinolin-2(1H)-ones and 3-aminocoumarins from 3-bromoquinolinones and 3-bromocoumarins, respectively, has been achieved. The reaction conditions involve the use of copper powder as the catalyst, eco-friendly ethanol as the solvent in the pres ence of pipecolinic acid as the ligand and ascorbic acid as the additive. The efficiency of this practical method was demonstrated in the synthesis of various anilines.
- Messaoudi, Samir,Brion, Jean-Daniel,Alami, Mouad
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experimental part
p. 1677 - 1687
(2010/10/01)
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- Studies on reaction of hydroxycoumarin compounds with formamide
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3-Hydroxycoumarin, on reaction with hot formamide, produced 3-formylaminocoumarin (2) which underwent deformylation on fusion with p-toluenesulphonic acid monohydrate to produce very pure variety of 3-aminocoumarin. 4-Hydroxycoumarin and 4-hydroxybenzo[b]thiopyran-2-one (7) on similar reaction produced benzo[l]pyrano[4,3-d]oxazol-4-one (6) and benzo[l]thiopyrano[4,3-d]oxazol-4-one (8) respectively, under effectively non-oxidising reaction condition.
- Ray, Sibdas,Paul, Subol Kr.
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p. 488 - 491
(2007/10/03)
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- Ortho-substituted anthranilic acid amides and their use as medicaments
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Ortho-substituted anthranilic acid amides and use thereof as pharmaceutical agents for treating diseases that are triggered by persistent angiogenesis are described.
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- Syntheses of diazadithiacrown ethers containing appended coumarin or 1-aminonaphthalene sidearms
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Six crown ethers containing two coumarin (11, 13, 14, 16, 17 and 19) or two 1-aminonaphthalene (15 and 20) fragments as sidearms and two crown ethers bearing one coumarin (12 and 18) arm were synthesized by a nucleophilic substitution of the secondary macrocyclic amine function on the alkyl halide. The major products of these reactions were the diazadithiacrown ethers containing two sidearms. In some cases, one-armed diazadithiacrown ethers were separated as minor products, although more than 2.5 mmoles of alkyl halide were used for 1.0 mmole of macrocyclic diamine.
- Song, Hua-Can,Chen, Yi-Wen,Yao, Jun-Hua,Xu, Zun-Le,Bradshaw, Jerald S.,Savage, Paul B.,Izatt, Reed M.
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p. 475 - 479
(2007/10/03)
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- New efficient synthesis of pyrido[2,3-c] and pyrido[3,2-c]coumarin derivatives
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Various substituted pyrido[2,3-c] and pyrido[3,2-c]coumarins are efficiently prepared in three steps from 3- and 4-hydroxycoumarins, respectively and protected β-aminoketones.
- Pavé, Grégoire,Chalard, Pierre,Viaud-Massuard, Marie-Claude,Troin, Yves,Guillaumet, Gérald
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p. 987 - 990
(2007/10/03)
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- META-GUANIDINE, UREA, THIOUREA OR AZACYCLIC AMINO BENZOIC ACID DERIVATIVES AS INTEGRIN ANTAGONISTS
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The present invention relates to a class of compounds represented by the Formula Ior a pharmaceutically acceptable salt thereof, whereinA ispharmaceutical compositions thereof and methods of using such compounds and compositions as alphavbeta3 antagonists.
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- Synthesis of 3-[α-(3-Chloro-2-oxo-4-substituted-phenyl/furfuryl-1-azetidinyl)]-2H-1- benzopyran-2-ones and 3-[α-(2-Substituted-phenyl/furfurylthiazolidiznyl)]-2H-1-benzopyran-2-ones as C.N.S. -active Agents
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Reaction of 3-substituted-phenylidine/furfurylidineamino-2H-1-benzopyran-2-ones (3a-d) with chloroacetyl chloride and thioglycolic acid affords the corresponding four-membered azetidinones (4a-d) and five-membered thiazolidinones (5a-d) respectively. All the compounds were tested for their acute toxicity, effects on gross behaviour, spontaneous motor activity (SMA), anorexigenic activity, neuroleptic activity and anticonvulsant activity. Compounds 4a and 5d exhibited C.N.S. depressant activity.
- Kulkarni,Srivastava,Bishnoi, Abha,Dua
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p. 173 - 175
(2007/10/03)
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- Haloalkyl derivatives of reporter molecules used to analyze metabolic activity in cells
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The subject invention provides substrates useful for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The substrates have the form wherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate, -REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properties different from those of the substrate, -SPACER- is a covalent linkage, and XR- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z-S-H) to form a thioether conjugate (Z-S-R-). After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.
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- Fluorescent haloalkyl derivatives of reporter molecules well retained in cells
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The subject invention provides a method for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The method for analyzing metabolic activity of cells involves the use of a substrate having the form wherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate, -REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properities different from those of the substrate, and XR-- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z--S--H) to form a thioether conjugate (Z--S--R--). After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.
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- PHOTOREACTIONS OF 4- AND 3-AZIDOCOUMARINS IN THE PRESENCE OF NUCLEOPHILES
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The photoreactions of 4-azidocoumarins (1) and 3-azidocoumarin (2) in the presence of nucleophiles such as alcohols, thiol or amines generally gave 4-substituted 3-amino- and/or 3-substituted 4-aminocoumarins, while pyrone ring fission with incorporation of two moles of nucleophile was observed in the reaction of 1 in the presence of primary or secondary aliphatic amine as a nucleophile.Plausible mechanisms for these reactions are suggested.
- Ito, Keiichi,Higuchi, Yukako,Tame, Chika,Hariya, Junko
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p. 937 - 947
(2007/10/02)
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- Synthesis and Study of Intramolecularly-quenched Fluorogenic Substrates Containing Aminocoumarin or Aminoquinolinone-type Fluorophores
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The amines 7-amino-4-methylcoumarin (AMec) (1), 7-amino-4-methyl-2-quinolinone (AMeq) (2) and 3-aminocoumarin (Ac) (3) have been used as fluorophores (H-F) and the aromatic systems 2,4-dinitrophenyl (Dnp), 2,4,6-trinitrophenyl (Tnp), 2-nitrophenylsulphenyl (Nps) and 3,5-dinitrobenzoyl (DnBz) have been used as quenchers (Q) in the synthesis of twelve intramolecularly-quenched fluorogenic substrates of general structure Q-Gly-Phe-F.The study of the fluorescence properties of the substrates synthesized shows that efficient quenching of fluorescence is observed in all cases.The Dnp, Nps and Tnp groups show a higher quenching efficiency and the combination of the Dnp group with the fluorophore Ac gives the best result (99percent quenching).The substrates synthesized can be used for the direct specific determination of enzymes which hydrolyse the peptide chain at any point between the interaction groups by measuring the increase in fluorescence.
- Kokotos, George,Tzougraki, Chryssa
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p. 495 - 499
(2007/10/02)
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- Synthesis of 3-(&α-Arylazo-benzylideneamino/furfurylideneamino)coumarins and Their Anti-inflammatory Activity
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3-(α-Arylazo-benzylideneamino/furfurylideneamino)coumarins (IVa-k) have been prepared by the coupling reaction of 3-arylidene-aminocoumarins (IIIa-c) with arenediazonium chlorides.The coumarins III in turn have been obtained by condensation of appropriate aldehydes with 3-aminocoumarin (II).An improved synthesis of 3-aminocoumarin (II) is also described.
- Kumar, Atul,Verma, M.,Saxena, A. K.,Shanker, K.
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p. 378 - 380
(2007/10/02)
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- A Facile Synthesis of 3-Acylaminocoumarins
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2-Methyl/phenyl-2-oxazolin-5-ones (2a,b), generated by cyclising aceturic and hippuric acids respectively with benzenesulphonyl chloride and triethylamine in benzene, undergo condensation with salicylaldehyde to give 3-acetyl/benzoylaminocoumarins (4a,b) which afford 3-aminocoumarin (5) on acid hydrolysis.Hydrolysis of 4b with KOH gives 3-hydroxycoumarin (6) and/or 2-benzoylamino-o-hydroxycinnamic acid (9).
- Tripathy, Pradeep K.,Mukerjee, Arya K.
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- Reactions of 2-Substituted 5-Oxazolones with Imines Carrying a Vicinal Hydroxyl Group & Salicylaldehyde
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5-Oxazolones, generated by cyclising N-acylglycines with ethyl chloroformate, react with imines carrying a vicinal hydroxyl group and also with salicylaldehyde.Unsaturated 5-oxazolone or 3-N-acylaminocoumarin is obtained depending on the type of reactants.
- Kumar, Pradeep,Mukerjee, Arya K.
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p. 704 - 707
(2007/10/02)
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