- UV derivative spectrophotometric study of the photochemical degradation of nisoldipine
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The photodecomposition of nisoldipine ((±)3-isobutyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylate), whereby its 4-(2-nitrosophenyl) pyridine analogue is obtained as the photolytic product, was investigated under daylight exposure by means of UV derivative spectrophotometry. The optimal instrumental parameters (120 nm/min scan speed; 2 nm slit width; Δλ=10 nm and 5 s response time) for analogue derivative spectra were established for amplitudes 1D285 and 2D291 (measured to the baseline) of the nitroso analogue assay, as well as for 1D386 of the parent compound-nisoldipine assay. Using the first-order derivative spectrum, the minimum detectable amount of nitroso analogue in the presence of nisoldipine was equivalent to an impurity level of 5% and by the second-order derivative spectrum, the determination limit was equivalent to an impurity level of 2%. The degradation of nisoldipine followed within 30 days and the calculated maximal degradation rate was 1.6% per day for nisoldipine raw material, but significantly lower values of 0.19 and 0.15% per day were obtained for Nisoldin tablets (10 and 5 mg, respectively). Copyright (C) 2000 Elsevier Science S.A.
- Marinkovic, Valentina,Agbaba, Danica,Karljikovic-Rajic, Katarina,Comor, Jozef,Zivanov-Stakic, Dobrila
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- Structural effects on the reactivity 1,4-dihydropyridines with alkylperoxyl radicals and ABTS radical cation
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A series of eight commercial C-4 substituted 1,4-dihydropyridines and other synthesized related compounds were tested for direct potential scavenger effect towards alkylperoxyl radicals and ABTS radical cation in aqueous Britton-Robinson buffer pH7.4. A direct quenching radical species was established. The tested 1,4-dihydropyridines were 8.3-fold more reactive towards alkylperoxyl radicals than ABTS cation radical, expressed by their corresponding kinetic rate constants. Furthermore, NPD a photolyte of nifedipine and the C-4 unsubstituted 1,4-DHP were the most reactive derivatives towards alkylperoxyl radicals. The pyridine derivative was confirmed by GC/MS technique as the final product of reaction. In consequence, the reduction of alkylperoxyl and ABTS radicals by 1,4-dihydropyridines involved an electron transfer process. Also, the participation of the hydrogen of the 1-position appears as relevant on the reactivity. Results of reactivity were compared with Trolox.
- Yanez,Lopez-Alarcon,Camargo,Valenzuela,Squella,Nunez-Vergara
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- Reactivity of C4-indolyl substituted 1,4-dihydropyridines toward superoxide anion (O2O) in dimethylsulfoxide
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Reactivity of two new C4-indolyl substituted 1,4-dihydropyridines (1,4-DHPs) toward superoxide anion (O2-) in dimethylsulfoxide (DMSO) is reported. Reactivity was followed by electrochemical and spectroscopic techniques. Gas chromatography-mass spectrometry (GC-MS) was used to identify the final products of the reaction. C4 indolyl-substituted-1,4-DHPs reacted toward O2O at significant rates, according to the calculated kinetic rate constants. Results are compared with 4-phenyl-DHP and the commercial 1,4-DHPs, nimodipine, nisoldipine, and amlodipine. Indolyl-substituted 1,4-DHPs were more reactive than the commercial derivatives. The direct participation of proton of the 1-position of the secondary amine in the quenching of O 2 was demonstrated.
- Salazar, Ricardo,Navarrete-Encina,Squella,Camargo,Nunez-Vergara, Luis J.
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- Reactivity of 1,4-dihydropyridines toward SIN-1-derived peroxynitrite
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Purpose. To study the reactivity of C4-substituted 1,4-dihydropyri- dines (1,4-DHP), with either secondary or tertiary nitrogen in the dihydropyridine ring, toward SIN-1-derived peroxynitrite in aqueous media at pH 7.4. Methods. Reactivity was followed by
- Lopez-Alarcon,Speisky,Squella,Olea-Azar,Camargo,Nunez-Vergara, Luis J.
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- Dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection (by machine translation)
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Relates to dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection, compounds such as nifedipine, amlodipine, Cini horizontal, Lacidipine, felodipine, NIKA of amlodipine, nitrendipine, nimodipine and BANI to equal, the method in acidic aqueous solution in the presence of a nickel-containing catalyst in the oxidation reaction of the then purified to realize. The method can be used for preparing this kind of drug detection and quality monitoring of the impurity reference substance, also can be used for quality detection process is used in the instrument of the instrument such as the dissolution of the design reference, drug synthesis process and the design of the manufacturing process of the preparation of the reference, in order to avoid impurities introduced by the process channels, in addition can also be dihydropyridine compound of related synthetic process route provides design provides a reference. The reaction can be in the acidic aqueous solution, to a suitable oxidant (such as air) as the oxidizing agent, in the presence of nickel, at normal temperature to carry out dehydrogenation aromatization reaction, mild reaction conditions, the target compound of high conversion rate, the operation is simple, by-product little small pollution to the environment, is a completely environment-friendly preparation process. (by machine translation)
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Paragraph 0092-0098
(2019/01/08)
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- Study on the oxidation of C4-phenolic-1,4-dihydropyridines and its reactivity towards superoxide radical anion in dimethylsulfoxide
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Electrochemical characterization on glassy carbon electrode (GCE) and reactivity with superoxide radical anion in aprotic medium of three new synthesized C4-phenolic-1, 4-dihydropyridines is reported. Voltammetry, coulometry, controlled-potential electrolysis (CPE), UV-vis spectroscopy, 1H NMR techniques were employed for the characterization of title compounds. The oxidation mechanism involves initially an oxidation process on the phenol moiety with the formation of the corresponding quinone followed by a second one affecting the dihydropyridine ring to give the pyridine derivative. Both processes appeared irreversible in character. Cyclic voltammetry was used to generate O2- by reduction on GCE of molecular oxygen in DMSO. The reactivity of DHPs towards O2- was directly measured by the anodic current decay of the radical in the presence of increasing concentration of tested 1,4-dihydropyridines and compared with the reaction of the reference antioxidant, Trolox. The linear correlations obtained between the anodic current of O2- and compound concentrations in the range between 0.01 mM and 1.00 mM allowed the determination of both the DHP antioxidant index (AI) and the concentrations needed to consume 50% of O2-. Synthesized C4-phenolic 1,4-dihydropyridines exhibited significant scavenging capacity towards superoxide radical anion higher than Trolox and tested commercial 1,4-dihydropyridines.
- Salazar, Ricardo,Navarrete-Encina,Squella,Barrientos,Pardo-Jiménez,Nú?ez-Vergara, Luis J.
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experimental part
p. 841 - 852
(2011/03/22)
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- Mild, selective, and high-yield oxidation of hantzsch 1,4-dihydropyridines with lead(IV) acetate
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Aromatization of 1,4-dihydropyridines with lead(IV) acetate under mild reaction conditions is described. The method is very selective, mild and versatile in the synthesis of different substituted pyridines.
- Litvic, Mladen,Cepanec, Ivica,Filipan, Mirela,Kos, Karmen,Bartolincic, Anamarija,Druskovic, Vinka,Tibi, Mohamed Majed,Vinkovic, Vladimir
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- Pyridyl compounds and pharmaceutical compositions containing them
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The present invention is concerned with new pyridine double esters of formula (I), their acids, and pharmaceutically acceptable salts. These compounds can be obtained by oxydation of the corresponding 1,4-dihydropyridines, and they are useful as cardioprotective agents in pharmaceutical compositions.
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- 2,2'-Bis(3-isobutyloxycarbonyl-5-methoxycarbonyl-2,6-dimethyl-4-pyridy l)-azobenzene-N,N'-dioxide: A new degradation product of nisoldipine by UV light
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The photochemical degradation of nisoldipine in UV light was investigated by means of HPLC and MS. A nitroso-product 2a, nitrophenylpyridine derivative 3a, two dimers of 2a could be identified as degradation products.
- Michelitsch,Reiner,Schubert-Zsilavecz,Likussar
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p. 548 - 549
(2007/10/02)
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- Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4
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A series of 21 different 4-substituted 2,6-dimethyl-3-(alkoxycarbonyl)-1,4-dihydropyridines was considered with regard to oxidation to pyridine derivatives by human liver microsomal cytochrome P-450 (P-450). Antibodies raised against P-450 IIIA4 inhibited the microsomal oxidation of nifedipine and felodipine to the same extent, as did cimetidine and the mechanism-based inactivator gestodene. Gestodene was ~ 103 times more effective an inhibitor than cimetidine, on a molar basis. When rates of oxidation of the 1,4-dihydropyridines were compared to each other in different human liver microsomal preparations, all were highly correlated with each other with the exceptions of a derivative devoid of a substituent at the 4-position and an N1-CH3 derivative. A P-450 IIIA4 cDNA clone was expressed in yeast and the partially purified protein was used in reconstituted systems containing NADPH-cytochrome P-450 reductase and cytochrome b5. This system catalyzed the oxidation of all of the 1,4-dihydropyridines except the two for which poor correlation was seen in the liver microsomes. Principal component analysis supported the view that most of these reactions were catalyzed by the same enzyme in the yeast P-450 IIIA4 preparation and in the different human liver microsomal preparations, or by a closely related enzyme showing nearly identical properties of catalytic specificity and regulation. The results indicate that the enzyme P-450 IIIA4 is probably the major human catalyst involved in the formal dehydrogenation of most but not all 1,4-dihydropyridine drugs.
- Guengerich,Brian,Iwasaki,Sari,Baarnhielm,Berntsson
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p. 1838 - 1844
(2007/10/02)
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