15362-40-0Relevant articles and documents
Vilsmeier reagent, NaHSe and diclofenac acid chloride: One-pot synthesis of a novel selenoindolinone with potent anticancer activity
Aydillo, Carlos,Plano, Daniel,Ruberte, Ana Carolina,Sanmartín, Carmen,Sharma, Arun K.
, p. 38404 - 38408 (2020)
An effective and straightforward synthesis of 3-seleno functionalized indolinone (5) involving Vilsmeier reagent is presented. Likewise, a procedure to achieve lactamization of diclofenac with excellent yields by using hydrides is also ascertained. Compou
Synthesis, ex vivo and in vitro hydrolysis study of an indoline derivative designed as an anti-inflammatory with reduced gastric ulceration properties
Chung, Man Chin,Dos Santos, Jean Leandro,Oliveira, Ednir Vizioli,Blau, Lorena,Renato Farina Menegon,Peccinini, Rosangela Goncalves
, p. 3187 - 3197 (2009)
The compound 1-(2,6-dichlorophenyl)indolin-2-one (1), planned as a pro-drug of diclofenac (2), was easily synthesized in 94% yield by an intramolecular reaction in the presence of coupling agent (i.e., EDC). Compound 1 showed anti-inflammatory and analgesic activity without gastro-ulcerogenic effects. The chemical and enzymatic hydrolysis profile of the lactam derivative 1 does not indicate conversion to diclofenac (2).This compound is a new non-ulcerogenic prototype for treatment of chronic inflammatory diseases.
Stability of diclofenac sodium in the inclusion complex with β-cyclodextrin in the solid state
Cwiertnia, Barbara,Hladon, Teresa,Stobiecki, Maciej
, p. 1213 - 1218 (1999)
The aim of this study was to characterize the thermal stability of diclofenac sodium both alone and in the inclusion complex with β-cyclodextrin in the solid state, by determination of the number of the products of its decomposition, which were identified by GC-MS. The molar ratio of diclofenac sodium in the inclusion complex with β-cyclodextrin was 1:1. The decomposition of diclofenac sodium both alone and in inclusion complex with β-cyclodextrin occurred according to the first-order reaction. The HPLC of the samples thermostated at 80°C gave five products of decomposition, which were identified by GC-MS. Diclofenac sodium in the inclusion complex with β-cyclodextrin was more thermally stable. Thermal decomposition of diclofenac sodium leads to formation of five products, of which 4-chloro-10H-9-acridinone had not been reported previously in the literature.
Diclofenac sodium injection sterilized by autoclave and the occurrence of cyclic reaction producing a small amount of impurity
Roy, Jiben,Islam, Mafizul,Khan, Anowar H.,Das, Subodh C.,Akhteruzzaman,Deb, Ajay K.,Mahbub Alam
, p. 541 - 544 (2001)
A known impurity is formed in the production of a parenteral dosage form of diclofenac sodium if terminally sterilized by autoclave. This impurity has been detected as 1-(2,6-diclorophenyl) indolin-2-one, which is also an intermediate from which diclofenac sodium is generally synthesized. It is only the condition of the autoclave method (i.e., 123 ± 2°C) that enforces the intramolecular cyclic reaction of diclofenac sodium forming the indolinone derivative and sodium hydroxide. The formation of this impurity has been found to depend on the initial pH of the formulation. The reaction follows first-order kinetics, and the energy of activation is 5.34 kcal/mol. The other excipients in the formulation do not have a role in this reaction. The concentration of the impurity in the resultant product in the ampule goes beyond the limit of the raw materials in the pharmacopoeias. It is thus preferable to use an alternative sterilization method; that is, an aseptic filtration method in which the formation of this impurity can be avoided.
Synthesis method of diclofenac sodium
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Paragraph 0024; 0026; 0028; 0030; 0032; 0034, (2021/09/21)
The invention discloses a synthesis method of diclofenac sodium, which comprises the following steps: (1) toluene. An oil layer is obtained by adding 2, 6 -dichlorophenol and sodium carbonate, keeping warm and refluxing, extracting the oil layer with water, and adding an alkali heat-preserving reaction in the oil layer to obtain 2, 6 -dichloroaniline. (2) 1, 2 Dichlorodimethylaniline prepared in step (6 -) is heated and melted, chloroacetyl chloride is added dropwise, and the heat is subjected to heat preservation reaction after being heated to crystallize to obtain N - (2, 6 - dichlorophenyl) - phenyl - chloroacetamide. (3) 2 (N - 2 Dichlorophenyl) 6 - phenyl - chloroacetamide prepared in step (-) is reacted with the aluminum trichloride to give a solid 1 - (2, 6 -dichlorophenyl) -2 -indolinone. (4) 3 (1 - 2-dichlorophenyl) 6 -indolinone prepared in step (-2 -) is added to alkali liquor, stirred and heated to reflux to obtain diclofenac sodium. The synthesis method is stable, easy to operate, low in cost, high in yield and suitable for industrial production.
Diclofenac n-derivatives as therapeutic agents with anti-inflammatory and anti-cancer effect
Galisteo, Alberto,Jannus, Fatin,García-García, Amalia,Aheget, Houssam,Rojas, Sara,Lupia?ez, José A.,Rodríguez-Diéguez, Antonio,Reyes-Zurita, Fernando J.,Quílez Del Moral, José F.
, (2021/05/18)
A series of diclofenac N-derivatives (2, 4, 6, 8c, 9c, 10a-c) were synthesized in order to test their anti-cancer and anti-inflammatory effects. The anticarcinogen activity has been assayed against three cancer cell lines: HT29, human colon cancer cells; Hep-G2, human hepatic cells; and B16-F10, murine melanoma cells. First, we determined the cytotoxicity of the different compounds, finding that the most effective compound was compound 8c against all cell lines and both compounds 4 and 6 in human Hep-G2 and HT29 cell lines. Compounds 4 and 8c were selected for the percentage of apoptosis determination, cell cycle distribution, and mitochondrial membrane potential measure because these products presented the lowest IC50 values in two of the three cancer cell lines assayed (B16-F10 and HepG2), and were two of the three products with lowest IC50 in HT29 cell line. Moreover, the percentages of apoptosis induction were determined for compounds 4 and 8c, showing that the highest values were between 30 to 60%. Next, the effects of these two compounds were observed on the cellular cycle, resulting in an increase in the cell population in G2/M cell cycle phase after treatment with product 8c, whereas compound 4 increased the cells in phase G0/G1, by possible differentiation process induction. Finally, to determine the possible apoptosis mechanism triggered by these compounds, mitochondrial potential was evaluated, indicating the possible activation of extrinsic apoptotic mechanism. On the other hand, we studied the anti-inflammatory effects of these diclofenac (DCF) derivatives on lipopolysaccharide (LPS) activated RAW 264.7 macrophages-monocytes murine cells by inhibition of nitric oxide (NO) production. As a first step, we determined the cytotoxicity of the synthesized compounds, as well as DCF, against these cells. Then, sub-cytotoxic concentrations were used to determine NO release at different incubation times. The greatest anti-inflammatory effect was observed for products 2, 4, 8c, 10a, 10b, and 9c at 20 μg·mL?1 concentration after 48 h of treatment, with inhibition of produced NO between 60 to 75%, and a concentration that reduces to the 50% the production of NO (IC50 NO) between 2.5 to 25 times lower than that of DCF. In this work, we synthesized and determined for the first time the anti-cancer and anti-inflammatory potential of eight diclofenac N-derivatives. In agreement with the recent evidences suggesting that inflammation may contribute to all states of tumorigenesis, the development of these new derivatives capable of inducing apoptosis and anti-inflammatory effects at very low concentrations represent new effective therapeutic strategies against these diseases.
Preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate
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Paragraph 0034-0034; 0038-0045, (2020/05/30)
The invention belongs to the field of chemical pharmacy, and relates to a production process of a chemical bulk drug, in particular to a preparation method of 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The preparation method comprises the following steps: taking 2, 6-dichlorodiphenylamine and chloroacetyl chloride as initial raw materials; and completing acylation reaction, Lewis acidicionic liquid catalyzed Friedel-Crafts alkylation reaction and hydrolysis reaction by a one-pot method to finally obtain the 2-[(2, 6-dichlorophenyl) amino] sodium phenylacetate. The 2-[(2,6-dichlorophenyl) amino] sodium phenylacetate is synthesized by adopting a one-pot preparation scheme, has the advantages of short reaction time, simplicity in operation, mild conditions, high yield, good catalytic effect, high selectivity, recyclability and the like, and is beneficial to industrial production.
Degradation kinetics and mechanism of diclofenac by UV/peracetic acid
Fu, Yongsheng,Liu, Yiqing,Zhang, Li
, p. 9907 - 9916 (2020/03/23)
In this work, the degradation kinetics and mechanism of diclofenac (DCF) by UV/peracetic acid (PAA) was investigated. The effects of pH, PAA dose and common water components such as inorganic ions and dissolved organic matter (DOM) on DCF degradation by UV/PAA were also evaluated. It was observed that the addition of PAA promoted the photodegradation of DCF due to the generation of reactive radicals in the photolysis of PAA, which was also confirmed by the radical scavenging experiment. The best degradation efficiency of DCF was obtained at pH 8.5. The removal of DCF was enhanced gradually with increasing PAA dose. Since NO3- is a photosensitive substance which can generate HO under UV irradiation, its existence promoted the degradation of DCF. The presence of CO32- could slightly improve DCF degradation, which might be due to the role of generated carbonate radicals. Cl-, SO42- and Fe3+ had little effect on DCF removal, while Cu2+ could enhance DCF degradation because of its catalytic ability for PAA decomposition. An inhibition effect on DCF removal was observed in the presence of DOM, and it was more obvious in higher concentration of DOM. The elimination of total organic carbon (TOC) was low. According to the twelve reaction products detected in the UV/PAA system, the probable transformation mechanism of DCF was proposed exhibiting eight reaction pathways, i.e., hydroxylation, decarboxylation, formylation, dehydrogenation, dechlorination-hydrogenation, dechlorination-cyclization, dechlorination-hydroxylation and amidation. This study indicates that UV/PAA is a promising method for DCF removal from contaminated water.
Isolation and structural characterization of degradation products of aceclofenac by HPLC, HRMS and 2D NMR
Guduru, Santhosh,Anji Karun Mutha,Vijayabhaskar,Kaliyaperumal, Muralidharan,Korupolu, Raghu Babu,Bonige, Kishore Babu,Rumalla, Chidananda Swamy
, p. 851 - 854 (2019/03/08)
The stability of aceclofenac under stress conditions was assessed to identify the degradation products. So, it was subjected to stress conditions like acid, base and oxidation, according to ICH guideline Q1A (R2). One degradation product formed when the drug was subjected to acid stress. Three degradation products were formed during the basic stress condition. The drug substance was found to be stable to oxidative stress. The degradants formed during the stress were separated on a C-18 column using gradient preparative HPLC elution. The only product (DP-2) formed during the acid stress and this one is same as of one of the three degradation products (DP-1, DP-2, DP-3) were formed during base stress. 1D and 2D NMR spectra and mass spectral analysis supported the proposed structures for the products. The products DP-2 and DP-3 have been reported earlier but this is the first report of product DP-1 as a degradation product of aceclofenac.
1 - Aryl -2 - indolinone derivatives preparation method
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Paragraph 0053-0060, (2019/04/18)
The invention discloses a method for synthesis of 1-aryl-2-indolinone derivatives. The method comprises the following steps: dissolving N-aryl-substituted phenylacetamide (III) in an organic solvent, adding a chlorination reagent and carrying out a reaction so as to obtain N-chloro-N-aryl-substituted phenylacetamid (II); and subjecting N-chloro-N-aryl-substituted phenylacetamid to a reaction with a certain amount of Lewis acid and a proper amount of an organic solvent at a certain temperature so as to obtain 1-aryl-2-indolinone (I). The method provided by the invention has the advantages of simple operation, easily available reagents, a low price, mild conditions and capability of synthesizing a plurality of 1-aryl-2-indolinone (I) compounds.
