91713-91-6Relevant articles and documents
Metabolic disposition of 14C-bromfenac in healthy male volunteers
Osman, Mohamed,Chandrasekaran, Appavu,Chan, Kelvin,Scatina, Jo Ann,Ermer, James,Cevallos, William,Sisenwine, Samuel F.
, p. 744 - 752 (1998)
The metabolic disposition of 14C-bromfenac, an orally active, potent, nonsteroidal, nonnarcotic, analgesic agent was investigated in six healthy male subjects after a single oral 50-mg dose. The absorption of radioactivity was rapid, producing a mean maximum plasma concentration (C(max)) of 4.9 ± 1.8 μg · equiv/mL, which was reached 1.0 ± 0.5 hours after administration. Unchanged drug was the major component found in plasma, and no major metabolites were detected in the plasma. Total radioactivity recovered over a 4-day period from four of the six subjects averaged 82.5% and 13.2% of the dose in the urine and faces, respectively. Excretion into urine was rapid; most of the radioactivity was excreted during the first 8 hours. Five radioactive chromatographic peaks, a cyclic amide and four polar metabolites, were detected in 0- to 24-hour urine samples. Similarity of metabolite profiles between humans and cynomolgus monkeys permitted use of this animal model to generate samples after a high dose for structure elucidation. Liquid chromatography/mass spectrometry (LC/MS) analysis of monkey urine samples indicated that the four polar metabolites were two pairs of diastereoisomeric glucuronides whose molecular weight differed by two daltons. Enzyme hydrolysis, cochromatography, and LC/MS experiments resulted in the identification of a hydroxylated cyclic amide as one of the aglycones, which formed a pair of diastereoisomeric glucuronides after conjugation. Data also suggested that a dihydroxycyclic amide formed by the reduction of the ketone group that joins the phenyl rings formed the second pair of diastereoisomeric glucuronides. Further, incubation of various reference standards in control (blank) urine and buffer with and without creatinine indicated that the hydroxy cyclic amide released from enzyme hydrolysis can undergo ex vivo transformations to a condensation product between creatinine and an α-keto acid derivative of the hydroxy cyclic amide that is formed by oxidation and ring opening. Further experiments with a dihydroxylated cyclic amide after reduction of the keto function indicated that it too can form a creatinine conjugate.
Role of Glucuronidation and P450 Oxidation in the Bioactivation of Bromfenac
Driscoll, James P.,Yadav, Aprajita S.,Shah, Nina R.
, p. 223 - 230 (2018)
Bromfenac is a nonsteroidal anti-inflammatory drug that was approved in the United States in 1997. It was withdrawn from clinical use less than one year later, in 1998, due to hepatotoxicity. We investigate the potential of bromfenac to be metabolized to reactive intermediates to further the current understanding of bromfenac bioactivation. Incubations were conducted with hepatocytes and human, rat, and cynomolgus liver microsomes fortified with cofactors and N-acetylcysteine. One thioether adduct of hydroxylated bromfenac and three thioether adducts of hydroxylated bromfenac indolinone were detected in extracts following incubations in liver microsomes fortified with NADPH and UDPGA. These findings demonstrate a bioactivation pathway for bromfenac and contribute to the body of evidence that could advance the understanding of the toxicity associated with bromfenac.
Bromfenac sodium intermediate purification system
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Paragraph 0011-0012, (2020/10/14)
The utility model discloses a bromfenac sodium intermediate purification system. The bromfenac sodium intermediate purification system comprises a washing device, a vacuum dryer and a purification device, the washing device comprises a water tank; a water inlet pipe and a water outlet pipe are respectively arranged at the upper part and the lower part of the water tank; the water inlet pipe is connected to a first tee joint; the drainage pipe is connected to the second tee joint; the first tee joint and the second tee joint are connected through a circulating pump; the other end of the first tee joint is connected with a pure water inlet valve; the other end of the second tee joint is connected with an external drainage valve; a filter basket is arranged on the inner side of the water tank; according to the bromfenac sodium intermediate purification system disclosed by the utility model, a 7-(4-bromobenzoyl)-1, 3-dihydro-2H-indole-2-ketone crude product is firstly washed with water, and vacuum drying is carried out after water washing is completed, so that primary purification is completed, and then secondary purification is carried out under a heating condition by virtue of a mixed solution of ethyl acetate and isopropanol, and the purification efficiency is high.
Preparation method of bromfenac sodium intermediate
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Paragraph 0030-0041; 0046-0047, (2019/09/05)
The invention belongs to the field of medicinal chemistry, and particularly relates to a preparation method of bromfenac sodium and an intermediate thereof. The method comprises the steps that a new solvent system is adopted for preparing the intermediate, generation of brick-red by-products is avoided, the impurity content in the intermediate is greatly reduced, and the purity and yield of the intermediate are improved.
A preparation method of a bromfenac sodium sesquihydrate compound
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Paragraph 0018; 0034; 0037; 0038, (2018/10/11)
A preparation method of a bromfenac sodium sesquihydrate compound is disclosed. The method includes steps of subjecting a compound of a formula 3 and an aqueous solution of sodium hydroxide to a hydrolysis reaction; directly subjecting the reaction solution to suction filtration after the reaction is completed; collecting a filtrate; adding sodium chloride or sodium bicarbonate into the filtrate;washing solid precipitated after the sodium chloride or sodium bicarbonate is added with saturated brine and acetone; performing recrystallization using a mixed solvent that is water/acetone, water/glycol dimethyl ether or water/ethylene glycol; and washing the solid obtained by recrystallization with acetone to obtain the bromfenac sodium sesquihydrate compound that is the compound of the formula4. The method is simple to operate and stable in process, and the obtained bromfenac sodium sesquihydrate compound is yellow solid with extremely high purity.
A bromide fragrant preparation method of sodium and important intermediates
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Paragraph 0049-0055, (2018/06/07)
The invention provides a preparation and refining method of bromfenac sodium. The method has the advantages that the reaction conditions are mild, the operation is simple, and the obtained product is high in purity, high in yield and low in cost and can be industrially produced easily.
A method for preparation of sodium bromine fragrance
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Paragraph 0040; 0071; 0075-0076, (2017/02/28)
The invention relates to a preparation method of bromfenac sodium. The preparation method comprises the following steps of (a) reacting a compound represented by a formula (V) with an electrophilic substitutional reagent in the presence of N,N-dimethylformamide or dimethyl sulfoxide to obtain a compound represented by a formula (IV), (b) adding the compound represented by the formula (IV) into 2-methoxyethanol, adding phosphoric acid and carrying out acid hydrolysis to obtain a compound represented by a formula (III), (c) hydrolyzing the compound represented by the formula (III) with sodium hydroxide, extracting with dichloromethane and adding acetic acid to neutralize to obtain a compound represented by a formula (II) and (d) in the presence of an organic alcohol solvent, adding a sodium hydroxide solution, hydrolyzing the compound represented by the formula (II) to form a salt, adding the organic alcohol solvent, cooling and crystallizing to obtain bromfenac sodium. According to the preparation method disclosed by the invention, the reaction yield of the intermediate (IV) and the quality of the product are improved, high-purity bromfenac sodium can be obtained just by virtue of crystallizing with the organic alcohol solvent, the good environmental benefit is achieved and the generation of bromfenac sodium polymer impurity is reduced.
Palladium-catalyzed direct addition of arylboronic acids to 2-aminobenzonitrile derivatives: Synthesis, biological evaluation and in silico analysis of 2-aminobenzophenones, 7-benzoyl-2-oxoindolines, and 7-benzoylindoles
Chen, Jiuxi,Ye, Leping,Su, Weike
supporting information, p. 8204 - 8211 (2015/01/08)
A palladium-catalyzed direct addition of arylboronic acids to unprotected 2-aminobenzonitriles has been developed, leading to a wide range of 2-aminobenzophenones with moderate to excellent yields. The transformation has broad scope and high functional group tolerance. Moreover, 2-oxoindoline-7-carbonitrile and indole-7-carbonitrile were applicable to this process for the construction of 7-benzoyl-2-oxoindolines and 7-benzoylindoles, respectively. Among the compounds examined, compound 4e possessed the most potent anticancer activity against H446 and HGC-27 in vitro, with IC50 values of 0.02 μmol L-1 and 0.09 μmol L-1, respectively, while compound 4a showed the best potent anticancer activity against SGC-7901 with an IC50 value of 0.01 μmol L-1. Furthermore, we also performed in silico molecular docking calculations to investigate the interaction mode and binding affinity between the examined compounds and their tubulin target. This journal is
Antiinflammatory agents. 3. Synthesis and pharmacological evaluation of 2-amino-3-benzoylphenylacetic acid and analogues
Walsh,Moran,Shamblee,Uwaydah,Welstead Jr.,Sancilio,Dannenburg
, p. 1379 - 1388 (2007/10/02)
A series of substituted derivatives of 2-amino-3-benzoylphenylacetic acid (amfenac) has been synthesized and evaluated for antiinflammatory, analgesic, and cyclooxygenase inhibiting activity. Several derivatives including 4'-chloro, 4'-bromo and 5-chloro, 4'-bromo were more potent than indomethacin in these assays.
