69002-84-2

Usage

Uses

Used in Pharmaceutical Industry:
5-HYDROXY DICLOFENAC is used as an active pharmaceutical ingredient for its potential therapeutic effects. As a metabolite of diclofenac, it may exhibit anti-inflammatory, analgesic, and/or antipyretic properties, which can be beneficial in the treatment of various conditions such as pain, inflammation, and fever.
Used in Research and Development:
5-HYDROXY DICLOFENAC is used as a research compound for studying its chemical properties, metabolic pathways, and potential applications in drug development. Its unique structure and properties make it an interesting subject for scientific investigation, which could lead to the discovery of new drugs or therapies.
Used in Quality Control and Analytical Testing:
5-HYDROXY DICLOFENAC is used as a reference standard or quality control material in the analysis and testing of pharmaceutical products. Its distinct chemical properties allow for accurate identification and quantification, ensuring the quality and safety of diclofenac-containing medications.
Used in Drug Metabolism Studies:
5-HYDROXY DICLOFENAC is used as a model compound in drug metabolism studies, helping researchers understand how the body processes and eliminates drugs. This knowledge can be applied to improve drug design, optimize dosing regimens, and predict potential drug interactions or side effects.
Used in Toxicology and Safety Assessment:
5-HYDROXY DICLOFENAC is used in toxicology and safety assessment studies to evaluate the potential risks and side effects associated with its use. Understanding its toxicity profile can help guide the development of safer and more effective medications based on its chemical structure.

InChI:InChI=1/C14H11Cl2NO3/c15-10-2-1-3-11(16)14(10)17-12-5-4-9(18)6-8(12)7-13(19)20/h1-6,17-18H,7H2,(H,19,20)

Upstream product

• 30267-40-4 1-(2',6'-dichlorophenyl)-1,3-dihydro-5-hydroxyindol-2-one 
• 15307-79-6 diclofenac sodium 
• 104-94-9 4-methoxy-aniline 
• 15307-86-5 [2-(2,6-dichloroanilino)phenyl]acetic acid 
• 70-18-8 GLUTATHIONE 
• 207395-03-7 N-(chloroacetyl)-2',6'-(dichlorophenyl)-4-(methoxyphenyl)amine 
• 696-62-8 para-iodoanisole 
• 100-17-4 para-methoxynitrobenzene 
• 100-02-7 4-nitro-phenol 
• 30124-19-7 2',6'-(dichlorophenyl)-4-(methoxyphenyl)amine 
• 30118-47-9 <2-(2,6-Dichlor-anilino)-5-methoxy-phenyl>-essigsaeure 
• 698357-92-5 2-[(2',6'-dichlorophenyl)amino]-5-methoxyphenyl-N,N-dimethylacetamide 
• 99540-20-2 (6-iodo-3-methoxy)phenyl-N,N-dimethylacetamide 
• 90526-08-2 2-(3-methoxyphenyl)-N,N-dimethylacetamide 

Downstream Products

• 30267-40-4 1-(2',6'-dichlorophenyl)-1,3-dihydro-5-hydroxyindol-2-one 
• 1285680-62-7 C₁₅H₁₃Cl₂NO₃ 

Relevant academic research and scientific papers

Electrochemical oxidation of diclofenac on CNT and M/CNT modified electrodes

The electrochemical oxidation of diclofenac (DCF), a non-steroidal anti-inflammatory drug considered as an emerging pollutant (frequently detected in wastewater), was investigated on CNT, Pt/CNT and Ru/CNT modified electrodes based on Carbon Toray in aqueous media. The electroreactivity of DCF on these modified electrodes was studied using cyclic voltammetry and the kinetic parameters were calculated from the scan rate study. Cyclic voltammograms show several oxidation processes, which confirm the interaction between DCF and the catalyst surface necessary for direct oxidation processes. Constant potential electrolysis of DCF was carried out on carbon nanotubes (CNT) and metal supported CNT (M/CNT) modified electrodes, in 0.1 M NaOH and 0.1 M Na2CO3/NaHCO3buffer media. The highest DCF conversion (88% after 8 h of electrolysis) was found in carbonate buffer medium, for Ru/CNT, while the best carbon mineralization efficiency (corresponding to 48% of the oxidized DCF) was obtained on Pt/CNT modified electrode in 0.1 M NaOH medium. The products of the electrolyses were identified and quantified by HPLC-MS, GC-MS, HPLC-UV-RID and IC. The results show the presence of some low molecular weight carboxylic acids, confirming the cleavage of the aromatic rings during the oxidation process.

TiO2-modified MALDI target for in vitro modeling of the oxidative biotransformation of diclofenac

The UV-induced photocatalytic oxidation in the presence of TiO2 nanoparticles (UV/TiO2-PCO) is a more adequate approach than electrochemical oxidation to simulate the oxidative metabolism of diclofenac based on the comparative analysis of oxidation products using high-resolution tandem mass spectrometry. A simple and fast high-throughput technique is proposed for modeling the oxidative metabolism, which involves UV/TiO2-PCO performed directly on a MALDI target and subsequent analysis by matrix-assisted laser desorption/ionization mass spectrometry. The ranges and yields of diclofenac oxidation products obtained by the conventional bulk UV/TiO2-PCO and the proposed on-target version are in excellent agreement.

Degradation of diclofenac, trimethoprim, carbamazepine, and sulfamethoxazole by laccase from Trametes versicolor: Transformation products and toxicity of treated effluent

The degradation of diclofenac (DCF), trimethoprim (TMP), carbamazepine (CBZ), and sulfamethoxazole (SMX) by laccase from Trametes versicolor was investigated. Experiments were conducted using the pharmaceuticals individually, or as a mixture at different initial concentrations (1.25 and 5 mg/L each). The initial enzymatic activity of all the treated samples was around 430–460 U(DMP)/L. The removal of the four selected pharmaceuticals tested individually was more effective than when tested in mixtures under the same conditions. For example, 5 mg DCF/L was completely removed to below its detection limit (1 μg/L) within 8 h in the individual experiment vs. after 24 h when dosed as a mixture with the other pharmaceuticals. A similar trend was visible with other three pharmaceuticals, with 95 vs. 39%, 82 vs. 34% and 56 vs. 49% removal after 48 h with 5 mg/L of TMP, CBZ, and SMX tested individually or as mixtures, respectively. In addition, at the lower initial concentration (1.25 mg/L each), the removal efficiency of TMP, CBZ, and SMX in mixtures was lower than that obtained at the higher initial concentrations (5 mg/L each) during both the individual and combined treatments. Four enzymatic transformation products (TPs) were identified during the individual treatments of DCF and CBZ by T. versicolor. For TMP and SMX, no major TPs were observed under the experimental conditions used. The toxicity of the solution before and after enzymatic treatment of each pharmaceutical was also assessed and all treated effluent samples were verified to be non-toxic.

Panel of New Thermostable CYP116B Self-Sufficient Cytochrome P450 Monooxygenases that Catalyze C?H Activation with a Diverse Substrate Scope

The ability of cytochrome P450 monooxygenases to catalyse a wide variety of synthetically challenging C?H activation reactions makes them highly desirable biocatalysts both for the synthesis of chiral intermediates and for late-stage functionalisations. However, P450s are plagued by issues associated with poor expression, solubility and stability. Catalytically self-sufficient P450s, in which the haem and reductase domains are fused in a single protein, obviate the need for additional redox partners and are attractive as biocatalysts. Here we present a panel of natural self-sufficient P450s from thermophilic organisms (CYP116B65 from A. thermoflava, CYP116B64 from A. xiamenense, CYP116B63 from J. thermophila, CYP116B29 from T. bispora and CYP116B46 from T. thermophilus). These P450s display enhanced expression and stability over their mesophilic homologues. Activity profiling of these enzymes revealed that each P450 displayed a different fingerprint in terms of substrate range and reactivity that cover reactions as diverse as hydroxylation, demethylation, epoxidation and sulfoxidation. The productivity of the bio-transformation of diclofenac to produce the 5-hydroxy metabolite increased 42-fold using the thermostable P450-AX (>0.5 g L?1 h?1) compared to the P450-RhF system reported previously. In conclusion, we have generated a toolkit of thermostable self-sufficient P450 biocatalysts with a broad substrate range and reactivity.

Drug Oxidation by Cytochrome P450BM3: Metabolite Synthesis and Discovering New P450 Reaction Types

There is intense interest in late-stage catalytic C-H bond functionalization as an integral part of synthesis. Effective catalysts must have a broad substrate range and tolerate diverse functional groups. Drug molecules provide a good test of these attributes of a catalyst. A library of P450BM3 mutants developed from four base mutants with high activity for hydrocarbon oxidation produced human metabolites of a panel of drugs that included neutral (chlorzoxazone, testosterone), cationic (amitriptyline, lidocaine) and anionic (diclofenac, naproxen) compounds. No single mutant was active for all the tested drugs but multiple variants in the library showed high activity with each compound. The high conversions enabled full product characterization that led to the discovery of the new P450 reaction type of oxidative decarboxylation of an α-hydroxy carboxylic acid and the formation a protected imine from an amine, offering a novel route to α-functionalization of amines. The substrate range and varied product profiles suggest that this library of enzymes is a good basis for developing late-stage C-H activation catalysts.

One-electron oxidation of diclofenac by human cytochrome P450s as a potential bioactivation mechanism for formation of 2′-(glutathion-S-yl)- deschloro-diclofenac

Reactive metabolites have been suggested to play a role in the idiosyncratic hepatotoxicity observed with diclofenac (DF). By structural identification of the GSH conjugates formed after P450-catalyzed bioactivation of DF, it was shown that three types of

Preparative microfluidic electrosynthesis of drug metabolites

In vivo, a drug molecule undergoes its first chemical transformation within the liver via CYP450-catalyzed oxidation. The chemical outcome of the first pass hepatic oxidation is key information to any drug development process. Electrochemistry can be used to simulate CYP450 oxidation, yet it is often confined to the analytical scale, hampering product isolation and full characterization. In an effort to replicate hepatic oxidations, while retaining high throughput at the preparative scale, microfluidic technology and electrochemistry are combined in this study by using a microfluidic electrochemical cell. Several commercial drugs were subjected to continuous-flow electrolysis. They were chosen for their various chemical reactivity: their metabolites in vivo are generated via aromatic hydroxylation, alkyl oxidation, glutathione conjugation, or sulfoxidation. It is demonstrated that such metabolites can be synthesized by flow electrolysis at the 10 to 100 mg scale, and the purified products are fully characterized.

Diclofenac derivatives with insulin-sensitizing activity

A series of diclofenac derivatives were synthesized. The insulin-sensitizing activity of 28 new compounds was evaluated in 3T3-L1 cells. The compounds 10a and 10f exhibited similar insulin-sensitizing activity with positive drug rosiglitazone.

Monooxygenation of aromatic compounds by dioxygen with bioinspired systems using non-heme iron catalysts and tetrahydropterins: Comparison with other reducing agents and interesting regioselectivity favouring meta-hydroxylation

Monooxygenation of aromatic compounds by dioxygen in the presence of catalytic amounts of an iron(II) salt and tetrahydropterins as reducing agents occurs with a regioselectivity favouring meta-hydroxylation of arenes bearing an electron-donating substituent, such as anisole, phenetole, toluene, and ethylbenzene. Comparison of similar systems using various reducing agents showed that only tetrahydropterins and ascorbate led to such a major meta-hydroxylation. The tetrahydropterin- and ascorbate-dependent systems should be useful for the preparation of meta-hydroxylated metabolites of aromatic drugs, as shown here in the case of diclofenac.

Syntheses and characterization of the acyl glucuronide and hydroxy metabolites of diclofenac

In humans, metabolism of the commonly used nonsteroidal antiinflammatory drug diclofenac 1 yields principally the 4′-hydroxy 2, 5-hydroxy 3, and acyl glucuronide 4 metabolites. All three metabolites have been implicated in rare idiosyncratic adverse react