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Liver Diseases
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Prehepatic drug-related jaundice may be produced directly by the administration of drugs such as phenylhydrazine, which causes hemolytic anemia by its action on red blood cells. The effects can be indirect, as with drugs such as primaquine, which induces hemolysis due to a genetically determined enzyme defect. There is a glucose 6-phosphate dehydrogenase deficiency in the erythrocytes of primaquine-sensitive individuals. In addition, the red blood cells are also deficient in glutathione and nicotinamide adenine dinucleotide. These cofactors are essential for the maintenance of cellular integrity. The metabolic consequence of the defect is that glutathione cannot be kept in the reduced state. This mechanism is implicated in the direct action of phenylhydrazine. Indirect effects causing hemolysis and bilirubin overload can occur when drugs are bound to the erythrocyte membrane. The effects of phenacetine and para-aminosalicylate are probably associated with this mechanism; these drugs also initiate the formation of antibodies and promote red blood cell agglutination and hemolysis.
The Second Half of the Nineteenth Century
Published in Arturo Castiglioni, A History of Medicine, 2019
Albrecht kossel (1853-1927), Hoppe-Seyler’s leading pupil and an eminent student of the chemistry of tissues, was the pioneer in the investigation of nucleic acids. It was he who originated the term “Bausteine” (building stones) for the amino acids, etc., in the metabolism of proteins. Kossel’s work, emphasizing the need for a more exact understanding of the complex components of protoplasm, leads us to perhaps the greatest of organic chemists, Emil fischer (1852-1919). In 1875 he discovered phenyl-hydrazine, the tool he used to advance the knowledge of sugars. Between 1883 and 1894 he had synthesized and supplied structural formulas for most of the common sugars and their isomers. In 1879-93 he synthesized numerous purines, including xanthine, and established the biochemical interrelationships of uric acid. In 1894 he supplied the “lock and key” concept for the specificity of enzyme activity. Having developed a hypersensitivity to phenylhydrazine, Fischer turned from sugar chemistry to the proteins. His work in this field established the structural nature of protein complexes, amino-acid units joined together by the “peptide bond.” He proved his point by the creation of synthetic polypeptides. Fischer’s accomplishments in this field, which have not been surpassed, were the harbinger of the great developments to come in the twentieth century.
A
Published in Anton Sebastian, A Dictionary of the History of Medicine, 2018
Antipyrin [Greek: anti, against + pyrexia, fever] Derivative of phenyl hydrazine, synthesized by Ludwig Knorr at the University of Würzburg in 1883. It was the first complete synthetic drug to be produced and was introduced into clinical practice as an antipyretic by Wilhelme Filehene in 1884. See antipyretics.
Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Hao He, Huifang Li, Toyosi Akanji, Shengli Niu, Zhujun Luo, Dongli Li, Navindra P. Seeram, Panpan Wu, Hang Ma
A series of OA derivatives were synthesised via structural modifications at OA’s C-2, C-3, C-28, C-12 and C-13 positions (Scheme 1). OA was first fluorinated with selectfluor (tetrafluoroborate) to obtain the intermediate analogue 3. Another intermediate analogue 4 was obtained by modifying compound 3 with the Jones reagent. The target compounds 5a-5c were prepared through condensation of compound 4 with various substituted phenylhydrazine and purified by column chromatography. Analogue 2 was synthesised by modifying OA at the C-3 position, which was oxidised to carbonyl with the Jones reagent. In addition, compounds 6a-6g were synthesised by employing a variety of substituted phenylhydrazine to compound 2 using the Fischer indolization approach. Similarly, target compounds 7a-7c and 8a-8c were synthesised through the condensation of compound 2 with various aldehydes via the Claisen Schmidt condensation. The structures of OA analogues were confirmed by their spectroscopic data including 1H NMR, 13 C NMR and HRMS.
Determination of the inhibitory effects of N-methylpyrrole derivatives on glutathione reductase enzyme
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Esma Kocaoğlu, Oktay Talaz, Hüseyin Çavdar, Murat Şentürk, Claudiu T. Supuran, Deniz Ekinci
Phenylhydrazine salts have been broadly used for modification of organic molecules with aryl groups. This synthetic procedure achieved transition metal free arylation of pyrrole in a eco-friendly way. The synthetic process started from the reaction of phenylhydrazine hydrochloride salt with NaOH to rapidly forma free phenylhydrazine, a slow oxidation with air to produce aryl radical15. Aryl radical X reacted with N-methyl pyrrole at room temperature to form allyl radical X which was supported by radical resonance after that losing a single electron loosing with air oxidation and eliminating a proton resulted acrylate pyrrole16.
Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Mohammed S. Abdel-Maksoud, Mohammed I. El-Gamal, Mahmoud M. Gamal El-Din, Chang Hyun Oh
Synthesis of the final compounds was achieved using the pathway illustrated in Scheme 1. Esterification of 3-methoxybenzoic acid (3) using methanol and Conc. sulphuric acid produced methyl 3-methoxybenzoate (4). Reaction of 4 with 2-bromo-4-methylpyridine in the presence of LiHMDS led to formation of 2-(2-bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (5). Compound 5 was refluxed with DMF-DMA to give (Z)-2-(2-bromopyridin-4-yl)-3-(dimethylamino)-1-(3-methoxyphenyl)prop-2-en-1-one (6), which further reacts with phenylhydrazine produced 2-bromo-4-(3-(3-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)pyridine (7). Compound 7 reacted with ethylenediamine or 1,3-propylenediamine to produce N1-(4-(3-(3-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)pyridin-2-yl)ethane-1,2-diamine (8) and N1-(4-(3-(3-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)pyridin-2-yl)propane-1,3-diamine (9). Reaction of compound 8 or 9 with the appropriate arylsulfonyl chloride in the presence of Et3N afforded the first group of final compounds 1a–i and 2a–i which bears the m-methoxyphenyl group at position 3 of the pyrazole ring. Demethylation of compounds 1a–i and 2a–i using boron tribromide produced corresponding hydroxyl derivatives 1j–q and 2j–q. An alternative pathway was investigated to synthesize the final compounds starting from compound 7. Arylation of N-(2-aminoethyl)benzenesulfonamide (10) or N-(3-aminopropyl)benzenesulfonamide (11) with compound 7 in the presence of pyridine at 110 °C led to formation of compounds 1a–i and 2a–i (Scheme 2).