- A convenient and expeditious synthesis of 3-(N-substituted) aminocoumarins via palladium-catalyzed Buchwald-Hartwig coupling reaction
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A convenient protocol for the rapid and efficient synthesis of 3-(N-substituted) aminocoumarins is described. The synthetic route developed involves the Pd-catalyzed C-N coupling reaction from readily available 3-bromocoumarin derivatives in the presence of the catalytic system Pd(OAc)2/Xantphos. Under these conditions, a series of nucleophiles including amides, sulfonamides, carbamates and functionalized amines, have been successfully reacted to afford the coupling products in fair to good yields.
- Audisio, Davide,Messaoudi, Samir,Peyrat, Jean-Fran?ois,Brion, Jean-Daniel,Alami, Mouad
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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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- 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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- Beckmann rearrangement: Thiamine hydrochloride as a remarkable catalyst for one-pot synthesis of amides from ketones
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Thiamine hydrochloride catalyzed synthesis of amides from ketones including 3-acetyl coumarin via Beckmann rearrangement has been reported. The reaction is believed to involve oxime formation, cleavage of C[sbnd]C bond followed by C[sbnd]N bond formation in one-pot. Thiamine hydrochloride is stable, cheap, easy to handle and environmentally friendly.
- Mahajan, Sheena,Slathia, Nancy,Kapoor, Kamal K.
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supporting information
(2020/04/08)
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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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- 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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- Evaluation of trypanocidal and antioxidant activities of a selected series of 3-amidocoumarins
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Background: Neglected diseases are becoming more prevalent due to globalization. This has inspired active research in the development of new drugs for the treatment of parasitic diseases such as Chagas disease. Objectives: With the aim of finding new tryp
- Moncada-Basualto, Mauricio,Lapier, Michel,Maya, Juan Diego,Matsuhiro, Betty,Olea-Azar, Claudio,Delogu, Giovanna L.,Uriarte, Eugenio,Santana, Lourdes,Matos, Maria Jo?o
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p. 573 - 584
(2018/08/17)
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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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p. 277 - 284
(2018/05/24)
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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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p. 1125 - 1132
(2018/03/02)
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- 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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supporting information
p. 2545 - 2552
(2018/10/21)
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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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- 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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- 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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supporting information
p. 5557 - 5561
(2016/11/11)
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- Copper(I)-promoted cycloalkylation-peroxidation of unactivated alkenes via sp3 C-H functionalisation
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A copper(i)-promoted cycloalkylation-peroxidation strategy has been developed via a three-component reaction involving cycloalkanes, tert-butyl hydroperoxide (TBHP) and internal conjugated alkenes possessing electron-withdrawing groups (EWGs). This process installs C-O and C-C bonds via sp3 C-H functionalisation with concomitant generation of two stereocentres. This regioselective radical addition of coumarin system is opposite to that of styrene.
- Banerjee, Arghya,Santra, Sourav Kumar,Mishra, Aniket,Khatun, Nilufa,Patel, Bhisma K.
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supporting information
p. 1307 - 1312
(2015/01/30)
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- Development of novel adenosine receptor ligands based on the 3-amidocoumarin scaffold
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With the aim of finding new adenosine receptor (AR) ligands presenting the 3-amidocoumarin scaffold, a study focusing on the discovery of new chemical entities was carried out. The synthesized compounds 1-8 were evaluated in radioligand binding (A1/
- Matos, Maria J.,Vilar, Santiago,Kachler, Sonja,Celeiro, Maria,Vazquez-Rodriguez, Saleta,Santana, Lourdes,Uriarte, Eugenio,Hripcsak, George,Borges, Fernanda,Klotz, Karl-Norbert
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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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supporting information
p. 5737 - 5742
(2015/11/24)
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- Targeting adenosine receptors with coumarins: Synthesis and binding activities of amide and carbamate derivatives
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Objectives With the aim of finding the structural features governing binding activity and selectivity against adenosine receptors (ARs), several 3-subtituted coumarins with amide (compounds 3-6) and carbamate (7-9) functions were synthesized. To study its possible influence on the binding activity and selectivity, a hydroxyl substituent was also introduced at position 4 of the coumarin moiety. Methods A new series of coumarins (3-9) were synthesized and evaluated by radioligand binding studies towards ARs. Key findings None of the 4-hydroxy derivatives (4, 8 and 9) showed binding affinity for any of the ARs. None of the compounds interacted with the hA2B AR (Ki > 100 000 nm). Compounds 3, 5, 6 and 7 had different activity profiles with dissimilar binding affinity and selectivity towards human A1, A 2A and A3 ARs. Conclusions The most remarkable derivative is compound 7, which presents the best affinity and selectivity for the A 3 adenosine receptor (Ki = 5500 nm).
- Matos, Maria Jo?o,Gaspar, Alexandra,Kachler, Sonja,Klotz, Karl-Norbert,Borges, Fernanda,Santana, Lourdes,Uriarte, Eugenio
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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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- FACE-selective fluorogenic cycloaddition reaction between coumarin azides and sugar terminal alkynes: An experimental and computational study
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Copper catalyzed azide-alkyne cycloaddition reaction (CuAAC) of non-fluorescent coumarin azides and sugar terminal alkynes afforded intense fluorescent 1,2,3-triazoles in 75-85% of yield. The photophysical properties of coumarin-sugar triazoles influenced greatly, upon introducing different substituents at 6th and 7th positions. The experimental observations were further supported by TD-DFT computational studies.
- Rajaganesh, Ramanathan,Ravinder, Pawar,Subramanian, Venkatesan,Mohan Das, Thangamuthu
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experimental part
p. 2327 - 2336
(2011/12/04)
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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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- Benzyne click chemistry: Synthesis of benzotriazoles from benzynes and azides
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(Chemical Equation Presented) A variety of substituted benzotriazoles have been prepared by the [3 + 2] cycloaddition of azides to benzynes. The reaction scope is quite general, affording a rapid and easy entry to substituted, functionalized benzotriazoles under mild conditions.
- Shi, Feng,Waldo, Jesse P.,Chen, Yu,Larock, Richard C.
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supporting information; experimental part
p. 2409 - 2412
(2009/05/11)
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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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p. 5077 - 5080
(2008/02/09)
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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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- PHENYL ISOTHIOCYANATE-MEDIATED CONDENSATION OF ACETURIC/2-ACETYLAMINOCINNAMIC ACID WITH AROMATIC ALDEHYDES
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One-flask synthesis of 4-arylmethylene-1-phenyl-2-styryl-2-imidazolin-5-ones (3) was achieved by the phenyl isothiocyanate-mediated condensation of aceturic/2-acetylaminocinnamic acid (1) with aromatic aldehydes (2).In the presence of salicylaldehyde (2d), the reaction of 1a and 5 led to the formation of 3-acetylaminocoumarin (4).
- Jain, Archana,Mukerjee, Arya K.
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p. 1521 - 1526
(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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