42771-81-3

Usage

Uses

Used in Pharmaceutical Industry:
Flurbiprofen Related Impurity 1 is used as an intermediate in the synthesis process for producing Flurbiprofen, an anti-inflammatory drug. Its role is crucial in the development of the final drug product, as it contributes to the overall efficacy and safety of the medication.
Used in Quality Control and Regulatory Compliance:
Flurbiprofen Related Impurity 1 is also used in the quality control and regulatory compliance processes within the pharmaceutical industry. By monitoring and controlling the presence of this impurity, manufacturers can ensure that the final product meets the required safety and efficacy standards, ultimately protecting patients from potential adverse effects.
Used in Research and Development:
In the field of research and development, Flurbiprofen Related Impurity 1 serves as a valuable compound for studying the properties and behavior of Flurbiprofen. This knowledge can be applied to improve the drug's formulation, optimize its delivery methods, and enhance its therapeutic potential.

Upstream product

• 71-43-2 benzene 
• 78543-08-5 2-(4-amino-3-fluorophenyl)-2-methylmalonic acid diethyl ester 
• 78543-06-3 diethyl 2-(3-fluoro-4-nitrophenyl)-2-methyl-malonate 
• 446-35-5 2,4-Difluoronitrobenzene 
• 609-08-5 Diethyl methylmalonate 
• 749917-24-6 2-(3-fluoro-4-iodophenyl)-2-methylmalonic acid diethyl ester 
• 98-80-6 phenylboronic acid 
• 149-73-5 trimethyl orthoformate 
• 497-19-8 sodium carbonate 
• 110-46-3 isopentyl nitrite 

Downstream Products

• 5104-49-4 fluorobiprofen 
• 42771-82-4 2-(2-fluoro-4-biphenylyl)-2-methylmalonic acid 
• 5104-49-4 (S)-(+)-flurbiprofen 
• 5104-49-4 (R)-flurbiprofen 

Relevant academic research and scientific papers

Targeted fluorination of a nonsteroidal anti-inflammatory drug to prolong metabolic half-life

In drug design, one way of improving metabolic stability is to introduce fluorine at a metabolically labile site. In the early stages of drug design, identification of such sites is challenging, and a rapid method of assessing the effect of fluorination on a putative drug's metabolic stability would be of clear benefit. One approach to this is to employ micro-organisms that are established as models of drug metabolism in parallel with the synthesis of fluorinated drug analogues. In this study, we have used the filamentous fungus Cunninghamella elegans to identify the metabolically labile site of the nonsteroidal anti-inflammatory drug flurbiprofen, to aid in the design of fluorinated derivatives that were subsequently synthesised. The effect of the additional fluorine substitution on cytochrome P450-catalysed oxidation was then determined via incubation with the fungus, and demonstrated that fluorine substitution at the 4′-position rendered the drug inactive to oxidative transformation, whereas substitution of fluorine at either 2′ or 3′ resulted in slower oxidation compared to the original drug. This approach to modulating the metabolic stability of a drug-like compound is widely applicable and can be used to address metabolic issues of otherwise good lead compounds in drug development. A metabolic stopper: By applying a chemical-microbiological approach to the design of drugs with enhanced metabolic stability, a series of fluorinated derivatives of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen was synthesised that were more resistant to cytochrome P450-catalysed transformation than the original drug.

Preparation of optically pure flurbiprofen via an integrated chemo-enzymatic synthesis pathway

In the synthesis of chiral molecules, the incorporation of enantioselective enzymatic conversions within the synthetic route often presents a useful approach. For the substitution of a chemical step with an enzymatic reaction, however, the complete synthetic route leading to and from this reaction needs to be considered carefully. An integrated approach, taking the possibilities and challenges of both types of conversions into account, can give access to chemo-enzymatic processes with great potential for effective synthesis strategies. We here report on the synthesis of enantiopure flurbiprofen using arylmalonate decarboxylase (AMDase, EC 4.1.1.76) in a chemo-enzymatic approach. Interestingly, practical considerations required shifting the enzymatic step to an earlier position in the synthetic route than previously anticipated. Engineered enzyme variants made it possible to obtain both (R)- and (S)-enantiomers of the target compound in excellent optical purity (>99%ee). The presented results underline that enzymes are most useful when they fit in a synthetic route, and that the optimization of biocatalytic steps and the planning of synthetic routes should be an integrated process.

PROCESS FOR PRODUCING BIARYL COMPOUND

A process for producing a biaryl compound, characterized by reacting an arylhydrazine compound, hydrogen peroxide and an aryl compound. When the reaction is conducted in the presence of a given metal or a compound of the metal or in the presence of a metal oxide obtained by reacting the given metal or a compound of the metal with hydrogen peroxide, then the yield of the biaryl compound is improved.

Process for preparing biaryl compounds via coupling of an arylamine with an arene

Improvement in the process for preparing biaryl compounds via coupling of an arylamine with an arene in the presence of a nitrite, an acid and copper metal or a derivative thereof; the improvement is consisting in adding to the reaction mixture a trialkylorthoformate. The process may be used for preparing drugs such as Flurbiprofen and Xenbucin or intermediate compounds particularly useful for preparing Flurbiprofen, Flufenisal, Chlordimorin, Xenbucin, Xenysalate, Xenyhexenic acid and the like.

Processes for the preparation of hydratropic acids and esters

The invention concerns the novel compounds dialkyl 2-(3-fluoro-4-nitrophenyl)-2-methylmalonate IIIa and dialkyl 2-(3-fluoro-4-aminophenyl)-2-methylmalonate IVa useful as intermediates in an improved process for making 2-(2-fluoro-4-biphenylyl)propionic acid, known as flurbiprofen, having the formula STR1 and ester thereof. It has anti-inflammatory activity which is about 240 times that of aspirin and analgesic activity which is about 180 times that of aspirin in standard laboratory tests. However, despite this high activity, the toxicity (LD50) is only 1.2 to 2.4 times greater than that of aspirin in standard laboratory tests. Also within the invention is a novel method of making the above intermediates and analogs thereof useful to prepare corresponding biaryl compounds which have pharmaceutical uses.

Therapeutically active phenylalkane derivatives

2-(2-Fluoro-4-biphenylyl)propan-1-ol, 2-(2'-Fluoro-4-biphenylyl)propan-1-ol and 2-(2,2'-Difluoro-4-biphenylyl)propan-1-ol Possessing great anti-inflammatory, analgesic and antipyretic activities.