32725-05-6Relevant academic research and scientific papers
Electron transfer processes in the reactivity of nonsteroidal anti-inflammatory drugs in the ground and excited states.
Moore,Ghebremeskel,Chen,Wong
, p. 685 - 691 (1998)
The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30 degrees C). The reaction was monitored spectrophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50 degrees C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.
From Alkyl Halides to Ketones: Nickel-Catalyzed Reductive Carbonylation Utilizing Ethyl Chloroformate as the Carbonyl Source
Shi, Renyi,Hu, Xile
supporting information, p. 7454 - 7458 (2019/04/30)
Ketones are an important class of molecules in synthetic and medicinal chemistry. Rapid and modular synthesis of ketones remains in high demand. Described here is a nickel-catalyzed three-component reductive carbonylation method for the synthesis of dialkyl ketones. A wide range of both symmetric and asymmetric dialkyl ketones can be accessed from alkyl halides and a safe CO source, ethyl chloroformate. The approach offers complementary substrate scope to existing carbonylation methods while avoiding the use of either toxic CO or metal carbonyl reagents.
Baeyer-Villiger Monooxygenase FMO5 as Entry Point in Drug Metabolism
Fiorentini, Filippo,Romero, Elvira,Fraaije, Marco W.,Faber, Kurt,Hall, Mélanie,Mattevi, Andrea
, p. 2379 - 2387 (2017/09/22)
Flavin-containing monooxygenases (FMOs) are emerging as effective players in oxidative drug metabolism. Until recently, the functions of the five human FMO isoforms were mostly linked to their capability of oxygenating molecules containing soft N- and S-nucleophiles. However, the human FMO isoform 5 was recently shown to feature an atypical activity as Baeyer-Villiger monooxygenase. With the aim of evaluating such an alternative entry point in the metabolism of active pharmaceutical ingredients, we selected and tested drug molecules bearing a carbonyl group on an aliphatic chain. Nabumetone and pentoxifylline, two widely used pharmaceuticals, were thereby demonstrated to be efficiently oxidized in vitro by FMO5 to the corresponding acetate esters with high selectivity. The proposed pathways explain the formation of a predominant plasma metabolite of pentoxifylline as well as the crucial transformation of the pro-drug nabumetone into the pharmacologically active compound. Using the recombinant enzyme, the ester derivatives of both drugs were obtained in milligram amounts, purified, and fully characterized. This protocol can potentially be extended to other FMO5 candidate substrates as it represents an effective and robust bench-ready platform applicable to API screening and metabolite synthesis.
FUNCTIONALISED AND SUBSTITUTED INDOLES AS ANTI-CANCER AGENTS
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Page/Page column 58, (2016/02/05)
The present invention relates to anti-tropomyosin compounds, processes for their preparation, and methods for treating or preventing a disease or disorder, such as a proliferative disease (preferably cancer), using compounds of the invention.
THERAPEUTIC PROSTAGLANDIN RECEPTOR AGONISTS
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Paragraph 0131, (2015/12/30)
Described herein are compounds which can be used in topical liquids, creams, or other dosage forms such as solids, for reducing intraocular pressure, treating glaucoma, growing hair, treating wounds, or other medical and/or cosmetic uses.
Fe-promoted cross coupling of homobenzylic methyl ethers with Grignard reagents via sp3 C-O bond cleavage
Luo, Shuang,Yu, Da-Gang,Zhu, Ru-Yi,Wang, Xin,Wang, Lei,Shi, Zhang-Jie
supporting information, p. 7794 - 7796 (2013/09/02)
The first iron-catalyzed formal cross coupling of homobenzylic methyl ethers with alkyl Grignard reagents is realized. The reaction is proposed to proceed through a sequence of dehydroalkoxylation to form the vinyl-intermediate, followed by Fe-catalyzed selective carbometalation to form a benzylic Grignard reagent.
An Efficient Synthesis of the Highly Tumorigenic anti-Diol Epoxide Derivative of Benzophenanthrene
Pataki, John,Raddo, Pasquale Di,Harvey, Ronald G.
, p. 840 - 844 (2007/10/02)
Synthesis of the potent tumorigen trans-3,4-dihydroxy-anti-1,2,3,4-tetrahydrobenzophenanthrene (1) in relatively few steps and superior overall yield is described.The method entails synthesis of the key intermediate 3-hydroxybenzophenanthrene (7b) v
