- A Primary Amide-Functionalized Heterogeneous Catalyst for the Synthesis of Coumarin-3-carboxylic Acids via a Tandem Reaction
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A crystalline primary amide-based bifunctional heterogeneous catalyst, {[Cd2(2-BPXG)(Fum)2(H2O)2]·2H2O}n (1) (where, 2-BPXG = 2,2′-((1,4-phenylenebis(methylene))bis((pyridin-2-ylmethyl)azanediyl)) diacetamide and Fum = fumarate), has been developed for the one-pot synthesis of a series of potentially biologically active coumarin-3-carboxylic acids at room temperature via a Knoevenagel-intramolecular cyclization tandem reaction. Catalyst 1 is prepared at room temperature from a one-pot self-assembly process in 81% yield and high purity within a few hours and has a ladder-like polymeric architecture based on single-crystal X-ray diffraction. Additional characterization of 1 includes elemental analysis, infrared spectroscopy, thermogravimetric analysis, and powder X-ray diffraction. Based on the optimized conditions, it is determined that 1 is highly efficient (conditions: 2 mol % catalyst, 3 h, and 26-28 °C in methanol) for this reaction. Its recyclability up to five cycles without significant loss of activity and structural integrity is also demonstrated. Using both electron-donating and electron-withdrawing substituents on the salicylaldehyde substrate, seven different derivatives of coumarin-3-carboxylic acid were made. Additionally, the monoamine oxidase (MAO) inhibitor, coumarin-3-phenylcarboxamide, has also been synthesized from coumarin-3-carboxylic acid obtained in the catalysis process. A detailed mechanism of action is also provided.
- Khullar, Sadhika,Mandal, Sanjay K.,Markad, Datta
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- Design, Synthesis, and Cholinesterase Inhibition Assay of Coumarin-3-carboxamide-N-morpholine Hybrids as New Anti-Alzheimer Agents
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A new series of coumarin-3-carboxamide-N-morpholine hybrids 5a–5l was designed and synthesized as cholinesterases inhibitors. The synthetic approach for title compounds was started from the reaction between 2-hydroxybenzaldehyde derivatives and Meldrum's acid to afford corresponding coumarin-3-carboxylic acids. Then, amidation of the latter compounds with 2-morpholinoethylamine or N-(3-aminopropyl)morpholine led to the formation of the compounds 5a–5l. The in vitro inhibition screen against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) revealed that most of the synthesized compounds had potent AChE inhibitory while their BuChE inhibitions are moderate to weak. Among them, propylmorpholine derivative 5g (N-[3-(morpholin-4-yl)propyl]-2-oxo-2H-chromene-3-carboxamide) bearing an unsubstituted coumarin moiety and ethylmorpholine derivative 5d (6-bromo-N-[2-(morpholin-4-yl)ethyl]-2-oxo-2H-chromene-3-carboxamide) bearing a 6-bromocoumarin moiety showed the most activity against AChE and BuChE, respectively. The inhibitory activity of compound 5g against AChE was 1.78 times more than that of rivastigmine and anti-BuChE activity of compound 5d is approximately same as rivastigmine. Kinetic and docking studies confirmed the dual binding site ability of compound 5g to inhibit AChE.
- Tehrani, Maliheh Barazandeh,Rezaei, Zahra,Asadi, Mehdi,Behnammanesh, Hossein,Nadri, Hamid,Afsharirad, Fatemeh,Moradi, Alireza,Larijani, Bagher,Mohammadi-Khanaposhtani, Maryam,Mahdavi, Mohammad
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- Monoamine oxidase A and B inhibitory activities of 3,5-diphenyl-1,2,4-triazole substituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives
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Monoamine oxidase (EC 1.4.3.4, MAO) is a flavin adenine dinucleotide-containing flavoenzyme located on the outer mitochondrial membrane and catalyzes the oxidative deamination of monoaminergic neurotransmitters and dietary amines. MAO exists in humans as two isoenzymes, hMAO-A and hMAO-B, which are distinguished by their tertiary structures, preferred substrates and inhibitors, and selective inhibition of these isoenzymes are used in the treatment of different diseases such as Alzheimer's, Parkinson's and depression. In the present study, we report the design, synthesis and characterization of 3,5-diphenyl-1,2,4-triazole substituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel and selective inhibitors of hMAO-B. Twenty one compounds (38, 39a-h, 41a-d, 42a-h) were screened for their inhibitory activity against hMAO-A and hMAO-B by using in vitro Amplex Red reagent based fluorometric method and all compounds were found to be as selective h-MAO-B inhibitors to a different degree. The compound 42e and 42h displayed the highest inhibitory activity against hMAO-B with IC50 values of 2.51 and 2.81 μM, respectively, and more than 25-fold selectivity towards inhibition of hMAO-B. A further kinetic evaluation of the most potent derivative (42e) was also performed and a mixed mode of inhibition of hMAO-B by the compound 42e was determined (Ki = 0,26 μM). According to our findings the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole emerged as a promising scaffold for the development of novel and selective hMAO-B inhibitors.
- ?etin, Mert,?ahin, Mehmet Eren,Bekircan, Olcay,Dan??, ?zkan
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- Method for synthesizing coumarin-3-carboxylic acid compounds by one-pot two-step method
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The invention relates to a method for synthesizing coumarin-3-carboxylic acid compounds by a one-pot two-step method. The structural formula of the coumarin-3-carboxylic acid compounds is shown in the description, wherein R1 is H , Cl , Br, NO2 , CH3 and HO . According to the synthesis process of the coumarin-3-carboxylic acid compounds, malonic acid, acetone and substituted salicylaldehyde serve as raw materials, iodine serves as a catalyst, acetic anhydride serves as a solvent, a series of coumarin-3-carboxylic acid compounds are synthesized through a one-pot cascade reaction, and the efficiency and the yield are greatly improved compared with a fractional step method.
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Paragraph 0053; 0056; 0058; 0067; 0079; 0084-0090
(2021/06/12)
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- Green synthesis method of coumarin-3-carboxylic acid compound
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The invention relates to a green synthesis method of a coumarin-3-carboxylic acid compound. The synthesis process of the coumarin-3-carboxylic acid compound is as follows: R1 is H, Cl, Br, NO2, CH3 and HO. A series of coumarin-3-carboxylic acid compounds are synthesized in one step without a catalyst by taking R1-substituted salicylaldehyde and Meldrum's acid as raw materials and water as a reaction medium, the process steps are simple, the method has universality, reaction liquid can be repeatedly added for reaction, no waste or waste liquid is generated, the yield of a target product is greater than 54.3%, and the method is an environment-friendly green synthesis method.
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Paragraph 0053-0061; 0067
(2021/06/26)
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- Synthesis of xanthene and coumarin derivatives in water by using β-Cyclodextrin
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Simple and green procedure was developed for the synthesis of various xanthene and coumarin derivatives using beta-cyclodextrin (β-CD) as reusable catalyst at 70?°C in water. Condensation of salicylaldehyde (1?mmol) and dimedone (2?mmol) or 1,3 cyclohexadione (2?mmol) gave corresponding xanthene derivatives, while condensation of salicylaldehyde (1?mmol) with Meldrum’s acid (1?mmol) or 4-Hydroxy-6-methyl-2H-pyran-2-one (1?mmol) gave respective coumarin derivatives in impressive yields. Involvement of β-CD as catalyst was ascertained by inclusion complex evaluation of β-CD-salicylaldehyde with 1H NMR analysis at 70?°C. Graphic abstract: [Figure not available: see fulltext.].
- Kamat, Siddharth R.,Mane, Ananda H.,Patil, Audumbar D.,Lohar, Trushant R.,Salunkhe, Rajashri S.
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p. 911 - 924
(2020/11/09)
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- Synthesis and biological evaluation of some 1,3-benzoxazol-2(3H)-one hybrid molecules as potential antioxidant and urease inhibitors
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A new series of 1,3-benzoxazol-2(3H)-one hybrid compounds, including coumarin, isatin 1,3,4-triazole and 1,3,4-thiadiazole moieties, were synthesized and biologically evaluated for their antioxidant capacities and anti-urease properties. The synthesized benzoxazole-coumarin (6a–e) and benzoxazole-isatin (10a–c) hybrids showed remarkable urease inhibitory activities with IC50 (μM), ranging from 0.0306 ± 0.0030 to 0.0402 ± 0.0030, while IC50 of standard thiourea is 0.5027 ± 0.0293. The synthesized benzoxazole-triazole (8a–c) and benzoxazole-thiadiazole (9a–c) hybrids showed similar urease inhibitory activities with IC50 (μM), ranging from 0.3861 ± 0.0379 to 0.5126 ± 0.0345. The antioxidant activity of the synthesized compounds was evaluated for their antioxidant activities, such as reducing power and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging. The results of ABTS radical scavenging activities of some of the synthesized molecules showed higher activities than standard Trolox, SC50 (μM) = 213.04 ± 18.12. One benzoxazole-coumarin (6f), two benzoxazole-isothiocyanate (7b, 7c), and two benzoxazole-triazole (8b, 8c) derivatives showed higher activities (SC50 (μM) values, 82.07 ± 10.34, 120.19 ± 7.30, 104.58 ± 10.55, 153.26 ± 7.14, and 144.82 ± 10.68, respectively) than standard Trolox, (SC50 (μM) = 213.04 ± 18.12).
- Yilmaz, Fatih,Mente?e, Emre,S?kmen, Bahar Bilgin
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p. 260 - 269
(2020/10/21)
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- Design, synthesis and biological evaluation of coumarin-based N-hydroxycinnamamide derivatives as novel histone deacetylase inhibitors with anticancer activities
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A series of novel coumarin-based N-hydroxycinnamamide derivatives were designed and synthesized as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds showed potent HDAC inhibitory activity and significant antiproliferative activity a
- Cheng, Maojun,Ding, Jiaoli,Fang, Yuanying,Guan, Zhiyu,Guo, Jie,Jin, Yi,Liu, Jing,Wan, Yang,Wang, Rikang,Xie, Sai-Sai,Zhang, Zhipeng
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- Synthesis and biological evaluation of carvacrol-based derivatives as dual inhibitors of H. Pylori strains and ags cell proliferation
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This study reports on the synthesis, structural assessment, microbiological screening against several strains of H. pylori and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis,1 H/13 C/19 F NMR spectra and crystallographic studies. The structure-activity relationships evidenced that among ether derivatives the substitution with specific electron-withdrawing groups (CF3 and NO2) especially in the para position of the benzyl ring led to an improvement of the antimicrobial activity, whereas electron-donating groups on the benzyl ring and ethereal alkyl chains were not tolerated with respect to the parent compound (MIC/MBC = 64/64 μg/mL). Ester derivatives (coumarin-carvacrol hybrids) displayed a slight enhancement of the inhibitory activity up to MIC values of 8–16 μg/mL. The most interesting compounds exhibiting the lowest MIC/MBC activity against H. pylori (among others, compounds 16 and 39 endowed with MIC/MBC values ranging between 2/2 to 32/32 μg/mL against all the evaluated strains) were also assayed for their ability to reduce AGS cell growth with respect to 5-Fluorouracil. Some derivatives can be regarded as new lead compounds able to reduce H. pylori growth and to counteract the proliferation of AGS cells, both contributing to the occurrence of gastric cancer.
- Sisto, Francesca,Carradori, Simone,Guglielmi, Paolo,Traversi, Carmen Beatrice,Spano, Mattia,Sobolev, Anatoly P.,Secci, Daniela,Di Marcantonio, Maria Carmela,Haloci, Entela,Grande, Rossella,Mincione, Gabriella
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- Novel coumarin-thiazolyl ester derivatives as potential DNA gyrase Inhibitors: Design, synthesis, and antibacterial activity
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The design and synthesis of novel coumarin-thiazolyl ester derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8p exhibited excellent antibacterial activity against four bacteria strains with MIC values of 0.05, 0.05, 8, and 0.05 μg/mL, respectively. In vitro drug-resistant bacterial inhibition experiments indicated that compound 8p exhibited the best bacteriostatic effect in the selected compounds and four positive control drugs with MIC values of 4 μg/mL. In vitro enzyme inhibitory assay showed that compound 8p exhibited potent inhibition against DNA gyrase with IC50 values of 0.13 μM. The molecular docking model indicated that compounds 8p can bind well to the DNA gyrase by interacting with amino acid residues. This study demonstrated that the compound 8p can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.
- Cheng, Xiang,Chu, Zhi-Wen,Hu, Rui,Liu, Hao,Lv, Xian-Hai,Xia, Dong-Guo
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- Zirconium(IV) oxychloride: A simple and efficient catalyst for the synthesis of chromen-2-one derivatives
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The present work explores a highly efficient, environmental friendly, green protocol for the synthesis of chromen-2-one derivatives (3a-m) by the condensation of salicylaldehydes with various active methylene compounds using zirconium (IV) oxychloride as catalyst. This is a convenient and rapid method for Knoevenagel condensation and this methodology offers several advantages including shorter reaction time, milder conditions, inexpensive catalyst, simple operational procedure and allowed to achieve the desired products in excellent yields. The structures of all the synthesized compounds were confirmed by spectral data.
- TASQEERUDDIN,ASIRI, YAHYA I.,SHAHEEN
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p. 2611 - 2616
(2020/10/22)
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- Evaluation of novel N′-(3-hydroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide derivatives as potential HIV-1 integrase inhibitors
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In an attempt to identify potential new agents that are active against HIV-1 IN, a series of novel coumarin-3-carbohydrazide derivatives were designed and synthesised. The toxicity profiles of these compounds showed that they were non-toxic to human cells and they exhibited promising anti-HIV-1 IN activities with IC50 values in nM range. Also, an accompanying molecular modeling study showed that the compounds bind to the active pocket of the enzyme.
- Jesumoroti, Omobolanle J.,Faridoon,Mnkandhla, Dumisani,Isaacs, Michelle,Hoppe, Heinrich C.,Klein, Rosalyn
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- Synthesis and Biological Evaluation of Some Succinimide Hybrid Molecules
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In this study, a new series of succinimide hybrid molecules containing isothiocyanate, coumarin, isatin, and furan moieties was synthesized and screened for α-glucosidase and antioxidant activities. Preliminary results revealed that all molecules showed good α-glucosidase inhibition effectiveness. Antioxidant activities of the hybrid molecules were determined using cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP) assays. Also, the radical scavenging activities of the synthesized compounds were assayed by using ABTS?+?and DPPH??methods. The results showed that all compounds exhibited moderated to high scavenging activity.
- Fatih Y?lmaz,Mente?e, Emre,Balta?, Nimet
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p. 575 - 584
(2020/01/21)
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- 3-substituted coumarin derivative and application and GPR35 receptor agonist
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The invention discloses a 3-substituted coumarin derivative and a pharmaceutically acceptable salt, a solvate, a hydrate or a crystal form. The compound of the invention generally exhibits high agonistic activity against human G protein-coupled receptor 35 (GPR35) and is specific agonists of the human GPR35 receptor. The compound provided by the invention is an active ligand of the novel GPR35 receptor, and the compound and the pharmaceutically acceptable salt, the solvate, the hydrate or the crystal form thereof generally exhibit higher activity and good selectivity to the human GPR35. The 3-substituted coumarin derivative is the specific agonist of the GPR35 receptor and can be used in the preparation of a medicament for treating, preventing and inhibiting a disease mediated by the GPR35receptor.
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Paragraph 0048; 0069; 0074-0075
(2018/06/04)
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- Novel coumarin-pyrazole carboxamide derivatives as potential topoisomerase II inhibitors: Design, synthesis and antibacterial activity
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The identification of novel Topoisomerase II (Topo II) inhibitors is one of the most attractive directions in the field of bactericide research and development. In our ongoing efforts to pursue the class of inhibitors, six series of 70 novel coumarin-pyrazole carboxamide derivatives were designed and synthesized. As a result of the evaluation against four destructive bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8III-k (MIC = 0.25 mg/L) showed considerable inhibitory activity than ciprofloxacin (MIC = 0.5 mg/L) against Escherichia coli and 8V-c (MIC = 0.05 mg/L) exhibited excellent antibacterial activity than ciprofloxacin (MIC = 0.25 mg/L) against Salmonella. The selected compounds (8III-k, 8V-c and 8V-k) exhibit potent inhibition against Topo II and Topo IV with IC50 values (9.4–25 mg/L). Molecular docking model showed that the compounds 8V-c and 8V-k can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial Topo II inhibiting bactericides.
- Liu, Hao,Ren, Zi-Li,Wang, Wei,Gong, Jie-Xiu,Chu, Ming-Jie,Ma, Quan-Wei,Wang, Jie-Chun,Lv, Xian-Hai
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- Peptides N-connected to hydroxycoumarin and cinnamic acid derivatives: Synthesis and fluorescence spectroscopic, antioxidant and antimicrobial properties
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The tripeptide Tyr-Gly-Ser and a series of conjugations to coumarin, cinnamic and gallic acid were synthesized in salt form and their antioxidant and antimicrobial activities were investigated. The N-connecting hydroxycoumarin, cinnamic and gallic acid derivatives to peptides and the use of BBr3 as a demethylating agent for peptides was reported. Their activities were investigated based on the conjugated moiety structures. Studies of their activities showed that conjugated tripeptides 7,8-dihydroxycoumarin-peptide (17), caffeic acid-peptide (22) and gallic acid-peptide (28) were found to be superior to ascorbic acid with respect to their antioxidant activity, and 12, 14, 24, and 25 exhibited the most antimicrobial activity in the series compared to amoxicillin. Additionally, the incredible florescence intensity and brightness of 17 in water and DMSO, compared to other synthesized compounds, qualified this peptide as a suitable probe in the human body.
- Ghalehshahi, Hajar G.,Balalaie, Saeed,Aliahmadi, Atousa
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p. 8831 - 8842
(2018/06/11)
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- Synthesis and characterisation of some new hybrid molecules containing thiophene, triazole and coumarin rings under microwave conditions
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In this work, a new series of N′-([4-amino-5-oxo-3-(thiophen-2-yl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl)-2-oxo-2H-1-benzopyran-3-carbohydrazides (thiophene–triazole–coumarin hybrid molecules) was synthesised from the reaction of 2-[4-amino-5-oxo-3-(thiophen-2-yl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetohydrazide and 3-(1H-benzotriazol-1-ylcarbonyl)-2H-chromen-2-ones by using microwave irradiation and conventional heating procedures and their results were compared. The reaction was performed using a very small amount of organic solvent and without using a catalyst.
- Yilmaz, Fatih
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p. 361 - 365
(2018/08/21)
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- Peroxy mediated Csp2-Csp3 dehydrogenative coupling: Regioselective functionalization of coumarins and coumarin-3-carboxylic acids
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A regioselective direct alkylation of coumarins at C-3 via cross-dehydrogenative coupling of unactivated Csp2-Csp3 bonds is developed. This protocol employs tert-butyl hydroperoxide as the sole reagent of the reaction to combine coumarins and ethers in reasonable yields under metal- and solvent-free reaction conditions. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a catalyst-free tandem alkylation/decarboxylation reaction with conservation of the double bond.
- Jafarpour, Farnaz,Darvishmolla, Masoumeh
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supporting information
p. 3396 - 3401
(2018/05/23)
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- Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents
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Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53–57.59?μM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50?=?0.80–14.81?μM) and HDAC1 inhibitory activity (IC50?=?0.47–0.87?μM and also, had no effect on Huvec (human normal cell line) viability (IC50?>?100?μM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47?±?0.02?μM near equal to the reference drug Entinostat (IC50?=?0.41?±?0.06?μM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzyme.
- Abdizadeh, Tooba,Kalani, Mohammad Reza,Abnous, Khalil,Tayarani-Najaran, Zahra,Khashyarmanesh, Bibi Zahra,Abdizadeh, Rahman,Ghodsi, Razieh,Hadizadeh, Farzin
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- Design and synthesis of novel Vitamin D-coumarin hybrids using microwave irradiation
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A series of novel vitamin D-coumarin hybrids were synthesised by esterification of the corresponding coumarin-3-carboxylic acids and vitamin D or vitamin D CD-ring alcohol in CH2Cl2 under microwave irradiation. They were obtained in higher yields (from 64-81% up to 79-87%) and shorter reaction time (from 3 h down to 15 min), compared with earlier conventional methodologies. The structures of all the target compounds were confirmed by 1H NMR, 13C NMR and HRMS. This provides an attractive and alternative method for the preparation of high-value vitamin D-coumarin hybrids.
- Zhang, Hengrui,Fang, Zhijie
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p. 684 - 687
(2018/01/08)
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- Synthesis and characterisation of some coumarin-1,2,4-triazol-3-thioether hybrid molecules
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A new series of N′-{[(4-methyl/phenyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio]acetyl}-2-oxo-2H-chromene-3-carbohydrazides was synthesised via the reaction of 2-[(4-methyl/phenyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio]acetohydrazides and 3-(1H-benzotriazol-1-ylcarbonyl)-2H-chromen-2-ones in good yields.
- Yilmaz, Fatih,Mente?e, Emre
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- Silver-Mediated Oxidative Decarboxylative Trifluoromethylthiolation of Coumarin-3-carboxylic Acids
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The introduction of trifluoromethylthio groups into organic compounds, in particular heterocycles, is important because of the prevalence of these structures in medicinally and agriculturally relevant molecules. Herein, the silver-mediated oxidative decarboxylative trifluoromethylthiolation of coumarin-3-carboxylic acids is reported. This methodology utilizes existing carboxylic acid functionalities for the direct conversion to CF3S groups and results in a broad scope of 3-trifluoromethylthiolated coumarins, including analogues of natural products, in moderate to excellent yields.
- Li, Minghao,Petersen, Jeffrey L.,Hoover, Jessica M.
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supporting information
p. 638 - 641
(2017/02/10)
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- Discovery of 2H-Chromen-2-one Derivatives as G Protein-Coupled Receptor-35 Agonists
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A family of 2H-chromen-2-one derivatives were identified as G protein-coupled receptor-35 (GPR35) agonists using dynamic mass redistribution assays in HT-29 cells. The compounds with 1H-tetrazol-5-yl in 3-substituted position displayed higher potency than the corresponding carboxyl analogs, and the hydroxyl group in the 7-position also played an important role in GPR35 agonistic activity. 6-Bromo-7-hydroxy-8-nitro-3-(1H-tetrazol-5-yl)-2H-chromen-2-one (50) was found to be the most potent GPR35 agonist with an EC50 of 5.8 nM. Calculating the physicochemical properties of compounds with moderate to high potency suggested that compounds 30, 50, and 51 showed good druggability. This study provides a novel series of GPR35 agonists, and compound 50 may be a powerful tool to study GPR35.
- Wei, Lai,Wang, Jixia,Zhang, Xiuli,Wang, Ping,Zhao, Yaopeng,Li, Jiaqi,Hou, Tao,Qu, Lala,Shi, Liying,Liang, Xinmiao,Fang, Ye
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p. 362 - 372
(2017/04/26)
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- Design and synthesis of some piperazine hybrid molecules
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In this work, a new series of piperazine hybrid molecules containing coumarin, isatin, salicyl, furane and 1,2,4-triazol-3- thiol moieties was synthesized in good yields. 2-[4-(4-Nitrophenyl)piperazin-1- yl]acetohydrazide was used as key intermediate to obtain these hybrid molecules. The structures of newly synthesized compounds were identified by 1H NMR, 13C NMR and elemental analysis data.
- Yilmaz, Fatih,Mente?e, Meltem
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p. 941 - 946
(2018/04/09)
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- Design, synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells
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A novel series of coumarin derivatives were designed, synthesized and investigated for inhibition of cholinesterase, including acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE). This biological study showed that these compounds containing piperazine ring had significant inhibition activities on AChE rather than BuChE. Further study suggested that 9x, as one of this kind of structure derivative, showed the strongest inhibition activity on AChE with an IC50 value of 34?nM. Moreover, molecular docking, flow cytometry (FCM), and western blot assay suggested that 9x could induce cytoprotective autophagy to attenuate H2O2-induced cell death in human neuroblastoma SH-SY5Y cells. These findings highlight a new approach for the development of a novel potential neuroprotective compound targeting AChE with autophagy-inducing activity in future Alzheimer's disease (AD) therapy.
- Yao, Dahong,Wang, Jing,Wang, Guan,Jiang, Yingnan,Shang, Lei,Zhao, Yuqian,Huang, Jian,Yang, Shilin,Wang, Jinhui,Yu, Yamei
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p. 112 - 123
(2016/08/01)
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- Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety
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A number of N-(2-(1H-indol-3-yl)ethyl)-2-oxo-2H-chromene-3-carboxamides were synthesized and tested against AChE and BuChE. The in?vitro assessment of the synthesized compounds 4a-o revealed that most of them had significant activity toward AChE. The SAR study demonstrated that the introduction of benzyloxy moiety on the 7-position of coumarin scaffold can improve the anti-AChE activity. The best result was obtained with 7-(4-fluorobenzyl)oxy moiety in the case of compound 4o, displaying IC50value of 0.16?μM. Based on the docking study of AChE, the prototype compound 4o was laid across the active site and occupied both peripheral anionic site (PAS) and catalytic anionic site (CAS).
- Ghanei-Nasab, Samaneh,Khoobi, Mehdi,Hadizadeh, Farzin,Marjani, Azam,Moradi, Alireza,Nadri, Hamid,Emami, Saeed,Foroumadi, Alireza,Shafiee, Abbas
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- A green chemical synthesis of coumarin-3-carboxylic and cinnamic acids using crop-derived products and waste waters as solvents
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Crop-derived products, like juices obtained from edible fruits and vegetables, and waste waters deriving from agricultural and industrial processing have been recently exploited to efficiently promote several ‘classic’ and innovative synthetic organic reactions. Such a green chemical approach prevented the use of toxic, polluting, and hazardous materials and in the mean time allowed to increase the commercial values of crop products and industrial byproducts. Coumarin-3-carboxylic and cinnamic acids represent classes of naturally occurring and semi-synthetic compounds with interesting and promising pharmacological activities. In this Letter a new and improved methodology for the Knoevenagel condensation yielding the title compounds using juices from edible fruits and vegetables (lemon, grapefruit, carrot, pomegranate, kiwi, vinegar, tomato), liqueurs (limoncello), and waste waters (buttermilk and residues of olive processing) as solvents is described. Coumarin-3-carboxylic and cinnamic acids have been synthesized in excellent yields by ultrasound irradiation from differently substituted 2-hydroxybenzaldehydes, 2-hydroxyacetophenones, and benzaldehydes, and Meldrum's acid as starting substrates. The findings described herein enforce the concept of the usefulness of products and byproducts derived from agriculture and food industry to accomplish green chemical processes.
- Fiorito, Serena,Taddeo, Vito Alessandro,Genovese, Salvatore,Epifano, Francesco
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supporting information
p. 4795 - 4798
(2016/10/05)
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- Et3N catalyzed cascade reaction of Meldrum’s acid with ortho-hydroxyaryl aldehydes for the synthesis of coumarin-3-carboxylic acids under solvent-less condition
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Abstract: The synthesis of coumarin-3-carboxylic acids in good yields is realized through a triethylamine catalyzed Knoevenagel-intramolecular cyclization tandem reaction of Meldrum’s acid with various ortho-hydroxyaryl aldehydes. This method expands the catalyst library about the synthesis of coumarin-3-carboxylic acids and also has advantages of using much less water as solvent, a cheap and eco-friendly catalyst, clean reaction conditions, simple workup procedure and easy isolation. Graphical Abstract: [Figure not available: see fulltext.]
- Pan, Wan-Yü,Xiao, Yü-Meng,Xiong, Hou-Qing,Lü, Cheng-Wei
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p. 7057 - 7063
(2016/08/25)
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- A cost-effective and green aqueous synthesis of 3-substituted coumarins catalyzed by potassium phthalimide
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An efficient procedure for the synthesis of various 2-imino-2H-chromene-3-carbonitriles, 2-oxo- 2H-chromene-3-carbonitriles as well as 2-oxo-2H-chromene-3-carboxylic acids is reported. It has been found that potassium phthalimide (PPI) catalyse the Knoevenagel condensation reaction of salicylaldehydes and activated β- dicarbonyl compounds efficiently under aqueous conditions at room temperature. This approach provides many merits such as high yields of products, clean, simple work-up, waste free, mild reaction conditions, commercially available organocatalyst, and the use of water as environmentally benign solvent.
- Kiyani, Hamzeh,Daroonkala, Masoumeh Darzi
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p. 449 - 456
(2015/10/19)
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- CONDENSATION PRODUCT OF THEANINE DERIVATIVE AND CARBOXYLIC ACID COUMARIN DERIVATIVE, INTERMEDIATE OF THE CONDENSATION PRODUCT, METHOD FOR PREPARING SAME, AND USE THEREOF
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The present invention relates to a compound as represented by formula (I), which is a condensation product of a theanine derivative and a carboxylic acid coumarin derivative, compounds as represented by formula (II) and formula (III), both of which are intermediates of the condensation product, a method for preparing these compounds, a pharmaceutical composition comprising the compounds, and a use thereof in preparing a medicament for prevention and treatment of tumors, inflammation, cardiovascular diseases, immune deficiency diseases and the like. Wherein, Wherein, Wherein.
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Paragraph 0073
(2015/09/22)
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- Synthesis and characterization of two novel biological-based nano organo solid acids with urea moiety and their catalytic applications in the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol), coumarin-3-carboxylic acid and cinnamic acid derivatives under mild and green conditions
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2-Carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid as novel, mild and biological-based nano organocatalysts with urea moiety were designed, synthesized and fully characterized by FT-IR, 1H NMR, 13C NMR, mass spectrometry, elemental analysis, thermal gravimetric, derivative thermal gravimetric, X-ray diffraction patterns, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, atomic force microscopy and UV/Vis analysis. The catalytic applications of 2-carbamoylhydrazine-1-sulfonic acid and carbamoylsulfamic acid were studied in the synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol), coumarin-3-carboxylic acid and cinnamic acid derivatives via the condensation reaction between several aromatic aldehydes and 1-phenyl-3-methylpyrazol-5-one (synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ols)), the Knoevenagel condensation of Meldrum's acid with salicylaldehyde derivatives (synthesis of coumarin-3-carboxylic acids) and the condensation of Meldrum's acid with aromatic aldehydes (synthesis of cinnamic acids) under mild and solvent-free conditions. In the presented studies, some products were formed and reported for the first time. The described nano organo solid acids have potential in industry.
- Zolfigol, Mohammad Ali,Ayazi-Nasrabadi, Roya,Baghery, Saeed
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p. 71942 - 71954
(2015/09/08)
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- Microwave-assisted synthesis of some new coumarin derivatives including 1,2,4-triazol-3-one and investigation of their biological activities
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By using the microwave technology, a new protocol has been developed for the synthesis of new coumarin derivatives including 1,2,4-triazol-3-one skeleton. This protocol proves to be efficient and environmentally friendly in terms of easy work-up and good yields. All newly synthesized compounds were screened for their antimicrobial activity and lipase inhibition. Most of the compounds were found to be effective on Escherichia coli. N'-{[4-Amino-3-(2-bromobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2H-chromene-3-carbohydrazide and N'-{[4-amino-3-(3,4-dichlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetyl}-6-bromo-2-oxo-2H-chromene-3-carbohydrazide had a good effect on lipase inhibition.
- Kahveci, Bahittin,Yilmaz, Fatih,Mente?e, Emre,ülker, Serdar
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p. 447 - 456
(2015/10/28)
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- Ultrasound-assisted sequential multicomponent strategy for the combinatorial synthesis of novel coumarin hybrids
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The present investigation reports an easy access to a library of novel spiro-oxindole-pyrrolizine or pyrrolo[1,2-c]thiazole fused coumarin hybrid heterocycles through a one-pot sequential four-component reactions of 2,2-dimethyl-1,3-dioxane-4,6-dione, salicylaldehydes, isatins, and cyclic α-amino acids under ultrasound irradiation.
- Kanchithalaivan, Selvaraj,Sumesh, Remani Vasudevan,Kumar, Raju Ranjith
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p. 566 - 572
(2014/12/10)
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- One-pot synthesis of coumarin-3-carboxamides containing a triazole ring via an isocyanide-based six-component reaction
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A facile, efficient, and environmentally friendly approach has been developed for the diversity oriented synthesis of trifunctional coumarin-amide-triazole containing compounds. A wide variety of pharmacologically significant and structurally interesting compounds were synthesized via a one-pot, six-component, tandem Knoevenagel/Ugi/click reaction sequence from readily available starting materials in ethanol at room temperature in excellent overall yields. Substituents could be independently varied at five different positions.
- Shaabani, Shabnam,Shaabani, Ahmad,Ng, Seik Weng
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p. 176 - 183
(2014/05/06)
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- Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors
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Abstract Some novel coumarin-3-carboxamide derivatives linked to N-benzylpiperidine scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The screening results showed that most of compounds exhibited potent anti-AChE activity in the range of nM concentrations. Among them, compound 10c bearing an N-ethylcarboxamide linker and a 6-nitro substituent showed the most potent activity (IC50 = 0.3 nM) and the highest selectivity (SI = 26,300). Compound 10c was 46-fold more potent than standard drug donepezil against AChE. The kinetic study revealed that compound 10c exhibited mixed-type inhibition against AChE. Protein-ligand docking study demonstrated that the target compounds have dual binding site interaction mode and these results are in agreement with kinetic study.
- Asadipour, Ali,Alipour, Masoumeh,Jafari, Mona,Khoobi, Mehdi,Emami, Saeed,Nadri, Hamid,Sakhteman, Amirhossein,Moradi, Alireza,Sheibani, Vahid,Homayouni Moghadam, Farshad,Shafiee, Abbas,Foroumadi, Alireza
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supporting information
p. 623 - 630
(2013/12/04)
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- Biological evaluation of coumarin derivatives as mushroom tyrosinase inhibitors
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A series of coumarin derivatives were synthesised and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that some of the synthesised compounds exhibited significant inhibitory activities. Especially, 2-(1-(coumarin-3-yl)ethylidene) hydrazinecarbothioamide bearing thiose-micarbazide group exhibited the most potent tyrosinase inhibitory activity with IC50 value of 3.44 μM. The inhibition mechanism analysis of 2-(1-(coumarin-3-yl)-ethylidene) hydrazinecarbothioamide and 2-(1-(6-chlorocoumarin-3-yl)ethylidene)- hydrazinecarbothioamide demonstrated that the inhibitory effects of the compounds on the tyrosinase were irreversible. Preliminary structure activity relationships' (SARs) analysis suggested that further development of such compounds might be of interest.
- Liu, Jinbing,Wu, Fengyan,Chen, Lingjuan,Zhao, Liangzhong,Zhao, Zibing,Wang, Min,Lei, Sulan
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p. 2872 - 2878
(2012/10/30)
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- Rapid synthesis of novel and known coumarin-3-carboxylic acids using stannous chloride dihydrate under solvent-free conditions
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Various coumarin-3-carboxylic acid (=2-oxo-2H-1-benzopyran-3-carboxylic acid; CcaH) derivatives have been synthesized in good yields using catalytic amounts of SnCl2·2 H2O under solvent-free conditions. This inexpensive, nontoxic, and readily available catalytic system (10 mol-%) efficiently catalyzes the Knoevenagel condensation and intramolecular cyclization of various 2-hydroxybenzaldehydes or acetophenones with Meldrum's acid. High product yields, use of inexpensive and safe catalyst, and solvent-free conditions display both economic and environmental advantages. Copyright
- Karami, Bahador,Farahi, Mahnaz,Khodabakhshi, Saeed
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experimental part
p. 455 - 460
(2012/05/04)
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- Potassium phosphate catalyzed efficient synthesis of 3-carboxycoumarins
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An efficient and rapid synthesis of 3-carboxycoumarins has been expediently accomplished by a reaction of salicylaldehyde with Meldrum's acid using potassium phosphate as an inexpensive catalyst at ambient temperature.
- Undale, Kedar A.,Gaikwad, Dipak S.,Shaikh, Tarannum S.,Desai, Uday V.,Pore, Dattaprasad M.
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experimental part
p. 1039 - 1042
(2012/10/08)
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- A green method for the synthesis of 3-substituted coumarins catalyzed by L-lysine in water via knoevenagel condensation
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L-lysine was applied to the synthesis of 3-substituted coumarins through the condensation of various salicylaldehyde with reactive methylene compounds in water. In this work, waste minimization, catalyst recovery, simple operation and easier product work-up were achieved.
- You, Xinwen,Yu, Hua,Wang, Mangang,Wu, Jun,Shang, Zhicai
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experimental part
p. 19 - 23
(2012/07/03)
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- Synthesis and Biological Evaluation of Coumarin Derivatives as Inhibitors of Mycobacterium bovis (BCG)
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The coumarin compounds are an important class of biologically active molecules, which have attractive caught the attention of many organic and medicinal chemists, due to potential pharmaceutical implications and industrial applications. We herein report t
- Rezayan, Ali Hossein,Azerang, Parisa,Sardari, Soroush,Sarvary, Afshin
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p. 929 - 936,8
(2020/08/24)
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- Synthesis, selective anti-Helicobacter pylori activity, and cytotoxicity of novel N-substituted-2-oxo-2H-1-benzopyran-3-carboxamides
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N-substituted-3-carboxamido-coumarin derivatives were prepared and evaluated for selective antibacterial activity against 20 isolates of Helicobacter pylori clinical strains, including five metronidazole resistant ones. Some of them possessed the best activity against H. pylori metronidazole resistant strains with MIC values lower than the drug reference (metronidazole). Furthermore, anti-inflammatory activity through the inhibition of the IL-8 production was investigated.
- Chimenti, Franco,Bizzarri, Bruna,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Granese, Arianna,Carradori, Simone,Rivanera, Daniela,Zicari, Alessandra,Scaltrito, M. Maddalena,Sisto, Francesca
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experimental part
p. 4922 - 4926
(2010/10/02)
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- Silica sulfuric acid: A versatile and reusable catalyst for synthesis of coumarin-3-carboxylic acids in a solventless system
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Synthesis of substituted coumarin-3-carboxylic acid via Knoevenagel condensation of meldrum's acid with ortho-hydroxyaryl aldehydes in solventless system is described.
- Hekmatshoar, Rahim,Rezaei, Akram,Beheshtiha, S. Y. Shirazi
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experimental part
p. 2491 - 2496
(2010/04/03)
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- A novel class of selective anti-Helicobacter pylori agents 2-oxo-2H-chromene-3-carboxamide derivatives
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A novel class of selective anti-Helicobacter pylori agents, 2-oxo-2H-chromene-3-carboxamide derivatives, were prepared and evaluated for their anti-bacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria and against various strains of pathogenic fungi. Some of them exhibited a potent and specific inhibitory effect on the growth of H. pylori, including metronidazole-resistant strains, in the 0.0039-16 μg/mL MIC range. A cytotoxic screening by the Trypan blue dye exclusion assay was also carried out on the most active compounds as anti-H. pylori agents. Among the derivatives examined for their cytotoxic potential, a number of them induced low cytotoxic effects.
- Chimenti, Franco,Bizzarri, Bruna,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Carradori, Simone,Granese, Arianna,Rivanera, Daniela,Lilli, Daniela,Zicari, Alessandra,Scaltrito, M. Maddalena,Sisto, Francesca
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p. 3065 - 3071
(2008/02/05)
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- Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: Biological activity and computational study
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A series of coumarin-3-acyl derivatives have been synthesized and investigated for the ability to inhibit selectively monoamine oxidases. The coumarin-3-carboxylic acids, 2a-e, proved to be reversible and selective inhibitors of the MAO-B isoform, display
- Chimenti, Franco,Secci, Daniela,Bolasco, Adriana,Chimenti, Paola,Granese, Arianna,Befani, Olivia,Turini, Paola,Alcaro, Stefano,Ortuso, Francesco
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p. 3697 - 3703
(2007/10/03)
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- An efficient solid-phase synthesis of 3-carboxycoumarins based on a scaffold-polymerbound cyclic malonic ester
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The condensation of substituted o-methoxybenzaldehydes or o-hydroxybenzaldehydes with a resin-bound cyclic malonic ester 3 afforded the resin 4 without catalyst. Cyclisation of the resin 4 in sulfuric acid formed 3-carboxycoumarins in good yield and excellent purity.
- Tang, Jing,Huang, Xian
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p. 354 - 355
(2007/10/03)
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- Coumarin synthesis via Knoevenagel condesation in moisture stable room temperature ionic liquids
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Several coumarins have been synthesised by Knoevenagel condesation in the piperidine/HOAc/moisture stable room temperature ionic liquid ([Emim] +BF4- referring to structure) system at room temperature; the yield of the reaction is good and the reaction medium can be recycled.
- Bao, Weiliang,Wang, Zhiming,Li, Yuxia
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p. 294 - 295
(2007/10/03)
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- A convenient synthesis of coumarin-3-carboxylic acids via Knoevenagel condensation of Meldrum's acid with ortho-hydroxyaryl aldehydes or ketones
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Coumarin-3-carboxylic acids were obtained in high yields with excellent purity from ortho-hydroxybenzaldehydes and Meldrum's acid after a 2 h reflux in ethanol. The less reactive ketones were first reacted with alcoholic ammonia to form ketimines, which were then condensed with Meldrum's acid to generate 4-alkylcoumarin-3-carboxylic acids in moderate yields.
- Song, Aimin,Wang, Xiaobing,Lam, Kit S.
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p. 1755 - 1758
(2007/10/03)
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- Solid phase synthesis of substituted coumarin-3-carboxylic acids via the Knoevenagel condensation
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A solid phase synthesis of substituted coumarin-3-carboxylates using the Knoevenagel condensation reaction between ethyl malonate bound to the Wang resin and ortho-hydroxyarylaldehydes is described. The reaction has been shown to proceed cleanly to give the desired products.
- Watson, Brett T.,Christiansen, Gerda E.
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p. 6087 - 6090
(2007/10/03)
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- Synthesis of Coumarin-3-O-acylisoureas by Dicyclohexylcarbodiimide
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The synthesis and isolation of some O-acylisoureas are described.The reaction between dicyclohexylcarbodiimide and coumarin-3-carboxylic acids leads to coumarin-dicyclohexylisourea derivatives, isolated as the main products, and to coumarin-dicyclohexylur
- Bonsignore, Leonardo,Cottiglia, Filippo,Maccioni, Anna M.,Secci, Daniela,Lavagna, Silvio M.
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p. 573 - 578
(2007/10/02)
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- SYNTHESIS OF 3-CARBOXYCOUMARINS FROM O-METHOXYBENZYLIDENE MELDRUM'S ACID DERIVATIVES
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Reaction of o-methoxybenzaldehydes with Meldrum's acid followed by cyclization in sulfuric acid of the benzylidene derivatives 3a-g affords 3-carboxycoumarins in excellent yields.
- Armstrong, Veronica,Soto, Oriana,Valderrama, Jaime A.,Tapia, Ricardo
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p. 717 - 726
(2007/10/02)
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