- Copper(II)-Catalyzed Tandem Reaction: Synthesis of Furo[3,2- c]coumarin Derivatives and Evaluation for Photophysical Properties
-
An efficient protocol for synthesizing furo[3,2-c]coumarin derivatives is described. The novel reaction could afford the desired furocoumarins with good to excellent yields in a mild and rapid manner. Large substrate scope screening and scale-up preparation have also been accomplished, and selected compounds were evaluated for their photophysical properties.
- Feng, Xi,Qin, Zhen,Cheng, Xinying,Liu, Dongyu,Peng, Yinghe,Huang, Huidan,Song, Bin,Bian, Jinlei,Li, Zhiyu
-
supporting information
p. 12537 - 12548
(2021/09/20)
-
- Synthesis and biological evaluation of bis-N2,N2′-(4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccinodihydrazides
-
A series of N2,N2′-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC50 = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.
- Hoppe, Heinrich C.,Isaacs, Michelle,Kaye, Perry T.,Krause, Rui W. M.,Manyeruke, Meloddy H.,Seldon, Ronnett,Tshiwawa, Thendamudzimu,Warner, Digby F.
-
-
- Synthesis and anti-inflammatory activity of 2-oxo-2H-chromenyl and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates
-
Cycloaddition reaction of 4-chloro-2-oxo-2H-chromene-3-carbaldehydes (3a-g) and 4-chloro-2H-chromene-3-carbaldehydes (7a-h) with activated alkynes (4a-b) provided the 2-oxo-2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (5a-n) and 2H-chromenyl-5-oxo-2,5-dihydrofuran-3-carboxylates (8a-p). All the prepared compounds were screened for anti-inflammatory activity. In vitro anti-inflammatory activity data demonstrated that the compounds 5g, 5i, 5k-l and 8f are effective among the tested compounds against TNF-α (1.108 ± 0.002, 0.423 ± 0.022, 0.047 ± 0.001, 0.070 ± 0.002 and 0.142 ± 0.001 μM) in comparison with standard compound Prednisolone (0.033 ± 0.002 μM). Based on in vitro results, three compounds (5i, 5k and 8f) have been selected for in vivo experiments and these compounds are identified as better compounds with respect to anti-inflammatory activity in LPS induced mice model. Compound 5i was identified as potent and showed significant reduction in TNF-α and IL-6.
- Bhimapaka, China Raju,Karri, Shailaja,Kuncha, Madhusudana,Kurma, Siva Hariprasad,Sistla, Ramakrishna
-
-
- Synthesis of substituted 4-(4-((3-Nitro-2-oxo-2H-chromene-4-yl)amino)phenyl)morpholine-3-one coumarin derivatives
-
A series of novel 4-(4-amino phenyl) morpholine-3-one substituted coumarin derivatives have been prepared by chloramine coupling reaction and were identified. The novel synthetic route involves nucleophilic substitution reaction of 4-chloro-3-nitro-2H-chromene-2- one with 4-(4-amino phenyl)morpholine-3-one. Due to the presence of nitro group in coumarin derivatives make substitution reaction easy and convenient at low temperature. Using DMF as solvent and K2CO3 as base various substituted 4-(4-((3-nitro-2-oxo-2H-chromen- 4-yl)amino)phenyl)morpholine-3-one derivatives (YS-1 to YS-10) can be obtain in good yield and high purity. Structural characterization of all synthesized compound was done by NMR, Mass and IR spectra.
- Sanghani, Yogesh J.,Koradiya, Suresh B.,Patel, Anilkumar S.
-
p. 1461 - 1464
(2019/06/11)
-
- Stereoselective synthesis of carbohydrate fused pyrano[3,2-c]pyranones as anticancer agents
-
Pyrano[3,2-c]pyranone is an important structural motif present in many natural products exhibiting diverse biological activities. Two series of carbohydrate fused pyrano[3,2-c]pyranone derivatives (n = 20) were efficiently synthesized starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxycoumarins in a very short reaction time (10 min) under microwave assisted conditions. The anticancer activity of these synthesized pyrano[3,2-c]pyranones was determined in detail through cellular assays against MCF-7 (breast), MDA-MB-231 (breast) and HepG2 (liver) cancer cell lines. The newly synthesized pyrano[3,2-c]pyranones were screened for their cell-viability and anti-proliferative activity against MCF-7, MDA-MB-231 and HepG2 cell lines. Compounds 12, 13 and 14 exhibited high growth inhibitory potencies selectively against MCF-7 cells with half-maximal inhibitory concentration (IC50) values of 19.9, 14.5 and 10.9 μM respectively. Compounds 12, 13, 14, 15 and 19 inhibited the growth of MDA-MB-231 cells (breast) by 43, 44, 37, 31 and 45% respectively. However, no inhibitory effect was observed for these compounds in the human liver cancer cell line (HepG2) and normal cell lines (HEK293, human embryonic kidney cells). Mechanistic studies showed that these compounds alter the cell morphology and cause G2/M arrest in MCF-7. Further studies showed that compounds 12, 13 and 14 significantly inhibited cell migration which was accompanied by altered microtubule distribution. An enhanced accumulation of these compounds in cells was observed as compared to the 4-hydroxycoumarins precursor in the intracellular uptake assay. These findings confirm that carbohydrate fused pyrano[3,2-c]pyranones are better candidates for anticancer activity.
- Kumari, Priti,Gupta, Sonal,Narayana, Chintam,Ahmad, Shakeel,Vishnoi, Nidhi,Singh, Shailja,Sagar, Ram
-
supporting information
p. 13985 - 13997
(2018/08/21)
-
- Synthesis of furo[3,2-c]coumarins via I2/TBHP-mediated reaction of 4-hydroxycoumarins with terminal alkynes
-
An efficient I2/TBHP-mediated process for the formation of furo[3,2-c]coumarins from readily available materials has been developed. This process for the formation of furo[3,2-c]coumarins is quite environmental friendly and atom-economical.
- Chu, Xianglong,Tang, Ziqiang,Ma, Jiangshan,He, Libowen,Feng, Lei,Ma, Chen
-
p. 970 - 974
(2018/02/09)
-
- Unexpected C-N bond formation via Smiles rearrangement: One pot synthesis of N -arylated coumarin/pyran derivatives
-
A conceptually new and one-pot method for the synthesis of N-arylated coumarin/pyran derivatives via Smiles rearrangement. The reaction of 4-bromocoumarin/pyran with 2-amino phenols affords O-arylated coumarin/pyran which subsequently rearranges into N-arylated coumarin/pyran under mild reaction conditions in good yields.
- Kumar, K. Shiva,Ramulu, Meesa Siddi,Kumar, N. Praveen
-
supporting information
p. 11276 - 11279
(2018/07/25)
-
- Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins and 1-aza-coumarins
-
A one pot three component, copper catalyzed azide-alkyne cycloaddition reaction has been employed for the synthesis of bis-coumarinyl triazoles (A–D) using 4-chloro, 4-bromomethyl, 3-bromoacetyl and 4-bromomethyl-1-aza-coumarins (I–IV), sodium azide, and coumarin propargyl ethers (V–IX) in moderate yields.
- Revankar, Hrishikesh M.,Kulkarni, Manohar V.
-
p. 537 - 544
(2018/01/10)
-
- One-pot two-step synthesis of 3-iodo-4-aryloxy coumarins and their Pd/C-catalyzed annulation to coumestans
-
An efficient protocol for the synthesis of various coumestans from the intramolecular annulation of 3-iodo-4-aryloxy coumarins through C-H activation has been developed. When 3-iodo-4-aryloxy coumarins were treated with 10% Pd/C (0.3 mol% Pd) in the presence of sodium acetate, the corresponding coumestans were produced in good to excellent yield. Reusability of the palladium catalyst was investigated in up to three consecutive cycles and it was found that the yield of the reaction was almost unaltered. Sequential iodination and O-arylation of 4-hydroxy coumarins leading to the 3-iodo-4-aryloxy coumarins were also achieved in a one-pot two-step process starting from aryl iodides in high yield. Pivalic acid was revealed to be the most effective additive for the later method to produce 3-iodo-4-phenoxy coumarins. Different functional groups bearing electron-donating as well as withdrawing groups are also tolerant to the reaction conditions.
- Panda, Niranjan,Mattan, Irshad
-
p. 7716 - 7725
(2018/03/01)
-
- Synthesis and biological evaluation of 4 arylcoumarin analogues as tubulin-targeting antitumor agents
-
The synthesis of twenty-six 4-arylcoumarin analogues of combretastatin A-4 (CA-4) led to the identification of two new compounds (25 and 26) with strong cytotoxic activity. Both compounds had a high cytotoxic effect on a CA-4-resistant colon adenocarcinoma cell line (HT29D4). The compounds affected cell cycle progression characterized by a mitotic block. The activity of these compounds against microtubules both in vitro and in cells was examined and both compounds were found to potently inhibit in vitro microtubule formation via a sub-stoichiometric mode like CA-4. By immunofluorescence, it was observed that both compounds induced strong microtubule network disruption. Our results provide a strong experimental basis to develop new potent anti-tubulin molecules targeting CA-4-resistant cancer cells.
- Mutai, Peggoty,Breuzard, Gilles,Pagano, Alessandra,Allegro, Diane,Peyrot, Vincent,Chibale, Kelly
-
p. 1652 - 1665
(2017/02/26)
-
- Convenient Michael addition/β-elimination approach to the synthesis of 4-benzyl- and 4-aryl-selenyl coumarins using diselenides as selenium sources
-
A concise and efficient, two-step approach toward 4-organoselenyl coumarin derivatives from the easily available 4-hydroxycoumarins, is reported. The synthesis was based on conventional tosylation followed by a tandem selena-Michael addition/β-elimination reaction of an aryl-/benzyl-selenolate anion on the corresponding 4-tosyloxycoumarins. The selenolate anions were conveniently generated in situ by exposure of the corresponding diselenides to NaBH4. Selected compounds demonstrated to exhibit antioxidant properties in mice cortex and hippocampus.
- Padilha, Gustavo,Birmann, Paloma T.,Domingues, Micaela,Kaufman, Teodoro S.,Savegnago, Lucielli,Silveira, Claudio C.
-
p. 985 - 990
(2017/02/15)
-
- Natural product Hirtellanine B and its derivatives in the preparation process for the preparation of medicine for treating tumor with the application of the
-
The present invention provides a preparation method of a natural product Hirtellanine B, wherein 2,4,6-trihydroxyacetophenone is adopted as a raw material, and steps of compound a preparation, compound b preparation, compound c preparation, compound d preparation, compound e preparation, compound f preparation, compound g preparation, and the like are performed to prepare the natural product Hirtellanine B. According to the present invention, biological activity screening is performed on Hirtellanine B and 14 Hirtellanine B derivatives, and results show that the natural product Hirtellanine B can inhibit proliferations of Jurkat cells, Raji cells and K562 cells, and the compounds provide a certain inhibition activity for tumor cells. The method has characteristics of easily available raw material, high reaction yield and reasonable operation, and is suitable for industrial production. The Hirtellanine B and the derivatives thereof can be used for preparing tumor treatment drugs, and have great clinical values. The natural product Hirtellanine B preparation method reaction formulas are as the follows.
- -
-
Paragraph 0051; 0137
(2016/10/10)
-
- Combined Claisen Rearrangement and Oxidative Cyclization as a Route to Hydroxymethyl Dihydrofuran-Annulated Coumarins
-
A convenient and simple method for the synthesis of novel 3,4-dihydrofuran-annulated coumarins, 3-(hydroxymethyl)-2H-furo[3,2-c]chromen-4(3H)-ones 5a, 5b, 5c, 5d, 5e, 5f, 5g, by combined Claisen rearrangement and intramolecular regioselective oxidative cyclization of 4-O-allyl coumarin intermediates 3a, 3b, 3c, 3d, 3e, 3f, 3g using inexpensive oxidizing agent m-CPBA is described. The reaction proceeds smoothly by tandem epoxidation/regioselective 5-exo-tet-intramolecular ring opening. The structures of synthesized compounds are established on the basis of spectral data including IR, 1H NMR, and mass and elemental analyses.
- Jayaprakash, Rao Y.,Chakravarthula, Venu
-
p. 1014 - 1018
(2015/08/06)
-
- Palladium-catalyzed [2+2+1] oxidative annulation of 4-hydroxycoumarins with unactivated internal alkynes: Access to spiro cyclopentadiene-chroman-2,4-dione complexes
-
Herein, we report our new results regarding a palladium-catalyzed [2+2+1] oxidative annulation of 4-hydroxycoumarins with unactivated internal alkynes, which affords a new class of compounds: the spiro cyclopentadiene-chroman-2,4- diones.
- Peng, Shiyong,Gao, Tao,Sun, Shaofa,Peng, Yanhong,Wu, Minghu,Guo, Haibing,Wang, Jian
-
supporting information
p. 319 - 324
(2014/05/20)
-
- Combining silver catalysis and organocatalysis: A sequential michael addition/hydroalkoxylation one-pot approach to annulated coumarins
-
A highly stereoselective one-pot procedure for the synthesis of five-membered annulated hydroxycoumarins has been developed. By merging primary amine catalysis with silver catalysis, a series of functionalized coumarin derivatives were obtained in good yields (up to 91%) and good to excellent enantioselectivities (up to 99% ee) via a Michael addition/hydroalkoxylation reaction. Depending on the substituents on the enynone, the synthesis of annulated six-membered rings is also feasible.
- Hack, Daniel,Chauhan, Pankaj,Deckers, Kristina,Hermann, Gary N.,Mertens, Lucas,Raabe, Gerhard,Enders, Dieter
-
supporting information
p. 5188 - 5191
(2014/12/11)
-
- Pd-catalyzed chemo-selective mono-arylations and bis-arylations of functionalized 4-chlorocoumarins with triarylbismuths as threefold arylating reagents
-
Cross-coupling reactions of differently substituted 4-chlorocoumarins were studied under palladium catalysis using triarylbismuths as threefold arylating reagents. The high reactivity of 4-chlorocoumarins was demonstrated delivering mono- and bis-arylation products in a chemo-selective manner. The reaction conditions employed are simple, robust and the threefold coupling reactivity of triarylbismuth reagents was witnessed with good to high yields in 2-4 h conditions. The utility of the methodology was explored in the synthesis of a few natural occurring neoflavones (3.27-3.30). In addition, the 4-arylcoumarin 3.1 product is a useful precursor for the preparation of (R)-tolterodine.
- Rao, Maddali L.N.,Kumar, Abhijeet
-
p. 6995 - 7005
(2015/03/14)
-
- Palladium-catalyzed oxidative annulation via C-H/N-H functionalization: Access to substituted pyrroles
-
Pyrroles, ubiquitous bioactive heterocycles in nature, are readily prepared via a palladium-catalyzed oxidative annulation of cyclic trans-enamines to various internal alkynes in the absence of a directing group. Copyright
- Peng, Shiyong,Wang, Lei,Huang, Jiayao,Sun, Shaofa,Guo, Haibing,Wang, Jian
-
supporting information
p. 2550 - 2557
(2013/10/21)
-
- Synthesis, characterization, and in vitro microbial evaluation of some new 4H-chromene and quinoline derivatives of 1H-pyrazole
-
A new series of nine derivatives of 4H-pyrano[3,2-c]chromene and 12 derivatives of N-thiazolyl-4H-quinoline of 1H-pyrazole has been synthesized by one pot base catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde, malononitrile, and 4-hydroxy coumarin or β-enaminones, respectively. All the synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR spectral data and were further screened, against a panel of pathogenic strains of bacteria and fungi.
- Thumar, Nilesh J.,Patel, Manish P.
-
p. 1169 - 1178
(2013/01/15)
-
- Subnanomolar inhibitor of cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues
-
Cytochrome bc1 complex (EC 1.10.2.2, bc1), an essential component of the cellular respiratory chain and the photosynthetic apparatus in photosynthetic bacteria, has been identified as a promising target for new drugs and agricultural fungicides. X-ray diffraction structures of the free bc1 complex and its complexes with various inhibitors revealed that the phenyl group of Phe274 in the binding pocket exhibited significant conformational flexibility upon different inhibitors binding to optimize respective π-π interactions, whereas the side chains of other hydrophobic residues showed conformational stability. Therefore, in the present study, a strategy of optimizing the π-π interaction with conformationally flexible residues was proposed to design and discover new bc1 inhibitors with a higher potency. Eight new compounds were designed and synthesized, among which compound 5c, with a Ki value of 570 pM, was identified as the most promising drug or fungicide candidate, significantly more potent than the commercially available bc1 inhibitors, including azoxystrobin (AZ), kresoxim-methyl (KM), and pyraclostrobin (PY). To our knowledge, this is the first bc1 inhibitor discovered from structure-based design with a potency of subnanomolar Ki value. For all of the compounds synthesized and assayed, the calculated binding free energies correlated reasonably well with the binding free energies derived from the experimental Ki values, with a correlation coefficient of r2 ) 0.89. The further inhibitory kinetics studies revealed that 5c is a noncompetitive inhibitor with respect to substrate cytochrome c, but it is a competitive inhibitor with respect to substrate ubiquinol. Due to its subnanomolar Ki potency and slow dissociation rate constant (k-0) 0.00358 s-1), 5c could be used as a specific probe for further elucidation of the mechanism of bc1 function and as a new lead compound for future drug discovery.
- Zhao, Pei-Liang,Wang, Le,Zhu, Xiao-Lei,Huang, Xiaoqin,Zhan, Chang-Guo,Wu, Jia-Wei,Yang, Guang-Fu
-
experimental part
p. 185 - 194
(2010/03/25)
-
- Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: Quinone oxidoreductase-1 (NQO1)
-
The synthesis is reported here of two novel series of inhibitors of human NAD(P)H quinone oxidoreductase-1 (NQO1), an enzyme overexpressed in several types of tumor cell. The first series comprises substituted symmetric dicoumarol analogues; the second series contains hybrid compounds where one 4-hydroxycoumarin systemis replaced by a different aromatic moiety. Several compounds show equivalent or improved NQO1 inhibition over dicoumarol, both in the presence and in the absence of added protein. Further, correlation is demonstrated between the ability of these agents to inhibit NQO1 and computed binding affinity. We have solved the crystal structure of NQO1 complexed to a hybrid compound and find good agreement with the in silico model. For both MIA PaCa-2 pancreatic tumor cells and HCT116 colon cancer cells, dicoumarol shows the greatest toxicity of all compounds. Thus, we provide a computational, synthetic, and biological platform to generate competitive NQO1 inhibitors with superior pharmacological properties to dicoumarol. This will allow a more definitive study of NQO1 activity in cells, in particular, its drug activating/detoxifying properties and ability to modulate oncoprotein stability. 2009 American Chemical Society.
- Nolan, Karen A.,Doncaster, Jeremy R.,Dunstan, Mark S.,Scott, Katherine A.,Frenkel, A. David,Siegel, David,Ross, David,Barnes, John,Levy, Colin,Leys, David,Whitehead, Roger C.,Stratford, Ian J.,Bryce, Richard A.
-
scheme or table
p. 7142 - 7156
(2010/07/20)
-
- Discovery and characterization of aminopiperidinecoumarin melanin concentrating hormone receptor 1 antagonists
-
4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2- one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evalu
- Kym, Philip R.,Iyengar, Rajesh,Souers, Andrew J.,Lynch, John K.,Judd, Andrew S.,Gao, Ju,Freeman, Jennifer,Mulhern, Mathew,Zhao, Gang,Vasudevan, Anil,Wodka, Dariusz,Blackburn, Christopher,Brown, Jim,Che, Jennifer Lee,Cullis, Courtney,Lai, Su Jen,LaMarche, Matthew J.,Marsilje, Tom,Roses, Jon,Sells, Todd,Geddes, Brad,Govek, Elizabeth,Patane, Michael,Fry, Dennis,Dayton, Brian D.,Brodjian, Sevan,Falls, Doug,Brune, Michael,Bush, Eugene,Shapiro, Robin,Knourek-Segel, Victoria,Fey, Thomas,McDowell, Cathleen,Reinhart, Glenn A.,Preusser, Lee C.,Marsh, Kennan,Hernandez, Lisa,Sham, Hing L.,Collins, Christine A.
-
p. 5888 - 5891
(2007/10/03)
-
- ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR
-
This invention provides compounds that are antagonists of melanin concentrating hormone receptor-1 (MCH-R1). The compounds are represented by formula (I): where m is zero or one, n is zero to two, Y is oxygen or -N (R9)-, R1, R2, R3, R4, R5, R9, and Ring A are defined in the specification. Coumarin and quinolone compounds where R1 and R2 together form a fused benzo ring are preferred. The invention also provides compounds of formula (VI) where the coumarin moiety is replaced by a quinazolinone ring. The compounds are useful for treating MCH-R1-related disorders, particularly overweight conditions including obesity.
- -
-
-
- Condensation of 2-hydroxyacetophenones with trichloroacetonitrile as a route to 2-trichloromethylchromones and 4-hydroxycoumarins
-
Condensation of 2-hydroxyacetophenones with trichloroacetonitrile in the presence of N-methylanilinomagnesium bromide affords hydroxyaryl β-amino-β-trichloromethylvinyl ketones, which are converted into 2-trichloromethylchromones upon treatment with concentrated HCl. The resulting compounds react with alcoholic solutions of NH3 or KOH to form 3-amino-1-(2-hydroxyaryl)-4,4,4-trichlorobut-2-en-1-ones and 4-hydroxycoumarins, respectively.
- Sosnovskikh,Kutsenko,Ovsyannikov
-
p. 478 - 481
(2007/10/03)
-
- SOME REACTIONS OF 6-CHLORO-2-METHYL-4H-1-BENZOPYRAN-4-ONE. I
-
4H-1-Benzopyran-4-ones (Chromones) are proved to be of special importance in medicine as stimulants of the central nervous system, spasmolytics, coronary dilators, inhibitors for the growth of human cancer cells, reductants for blood pressure, diuretics, antiallergic, antibiotics and cardiovascular agents. In the course of the present work several new derivatives containing the chromone moiety were prepared. Some of their reactions were investigated in the hope of obtaining new compounds having biological activities. The reactivities of chromone nucleus towards cycloaddition reactions under Diels-Alder conditions, nucleophilic and electrophilic reagents, photocyclodehydrogenation and thiation have been investigated.
- Salem, Mounir A. I.,Hamed, Ashraf A.,El-Shekeil, Ali G.,Babaqui, A. S.,Madkour, Hassan M. F.
-
p. 495 - 508
(2007/10/03)
-
- A NEW AND CONVENIENT SYNTHESIS OF 3-HYDROXYCHROMONES
-
An improved synthesis of 3-hydroxychromones is described.
- Rao, Ch. Prasad,Srimannarayana, G.
-
p. 1507 - 1512
(2007/10/02)
-
- Coumarin derivatives for the treatment of allergies
-
Pharmaceutical compositions for the treatment of allergies are produced using coumarin derivatives as the active agent. Certain of these compounds and their salts are novel.
- -
-
-
