- Efficient drug metabolism strategy based on microsome-mesoporous organosilica nanoreactors
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A rapid and accurate in vitro drug metabolism strategy has been proposed based on the design of a biomimetic nanoreactor composed of amino-functionalized periodic mesoporous organosilica (NH2-PMO) and microsomes. The amphiphilic nature and posi
- Fang, Xiaoni,Zhang, Peng,Qiao, Liang,Feng, Xiaoyan,Zhang, Xiangmin,Girault, Hubert H.,Liu, Baohong
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- A highly selective H/D exchange reaction of 1,4-dihydropyridines
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Herein, we report a simple, economical, and effective acid-mediated method for the in situ deuteration of Hantzsch esters and their 4-substituted derivatives, including some drugs that constitute important calcium channel blockers which are effective for
- Wang, Kaiqian,Chen, Xiaoping,Peng, Xiao,Wang, Ping,Liang, Feng
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supporting information
p. 3845 - 3852
(2019/04/26)
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- CO2-Catalyzed Efficient Dehydrogenation of Amines with Detailed Mechanistic and Kinetic Studies
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CO2-catalyzed dehydrogenation of amines has been achieved under photocatalytic conditions. With this concept, various amines have been selectively dehydrogenated to the corresponding imines in the presence of different functional groups such as nitrile, nitro, ester, halogen, ether, thioether, and carbonyl or carboxylic acid moieties. At the end, the CO2-catalyzed synthesis of pharmaceutical drugs has been achieved. The CO2 radical has been detected by EPR spectroscopy using DMPO, and the mechanism of this reaction is proposed on the basis of DFT calculations and experimental evidence.
- Riemer, Daniel,Schilling, Waldemar,Goetz, Anne,Zhang, Yu,Gehrke, Sascha,Tkach, Igor,Hollóczki, Oldamur,Das, Shoubhik
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p. 11679 - 11687
(2018/11/23)
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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 0056-0062
(2019/01/08)
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- N3,N6-BIS(2-(5-METHOXY-1H-INDOLE-3-YL)ETHYL)-2,6-DIMETHYL-4-(2-NITROPHENYL)PYRIDINE-3,5-DICARBOXAMIDE AND USE THEREOF IN THE FIELD OF NEUROTOXICITY
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The invention relates to a molecule enabling removal of neurotoxicity observed in neuron cells due to various reasons.
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Page/Page column 4; 5
(2017/08/21)
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- For 1, 4 - dihydro pyridine compound to prepare the corresponding pyridine compound (by machine translation)
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The invention discloses a method for the 1, 4 - dihydro pyridine compound to prepare the corresponding pyridine compound. The method of the invention is: will be 1, 4 - dihydro pyridine compound, eosin Y of the four n-butyl ammonium salt, potassium carbonate is added to the organic solvent with the water in the mixed solvent of stirring and mixing, inject the air in visible light irradiation under the conditions of reaction, to be after the reaction, by adding ethyl acetate, respectively water, saturated ammonium chloride washing, removal of inorganic alkali and adjust the system to subacid, in the organic phase by adding a small amount of activated carbon to remove the pigment, then dried with anhydrous sodium sulfate, turns on lathe does, recrystallize and obtain the corresponding pyridine compound. The method of the invention compared with the prior art has to oxygen in air as the oxidizing agent, is cheap and easy to get; to sunlight as the energy source, so that the industrial production more favorable; catalytic amount of the use of non-metal catalyst, reduces the cost of synthesizing, avoiding the noble metal in the accumulation of drug in the synthesis. (by machine translation)
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Paragraph 0014-0016
(2017/08/19)
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- Acetylshikonin is a novel non-selective cytochrome P450 inhibitor
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Acetylshikonin is a biologically active compound with anti-cancer and anti-inflammatory activity, which is isolated from the roots of Lithospermum erythrorhizoma. An inhibitory effect of acetylshikonin against CYP2J2 activity was discovered recently. Based on this result, this study was expanded to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed a strong inhibitory effect against all P450s tested with IC50 values of 1.4–4.0 μ m. Pre-incubation of acetylshikonin with HLMs and NADPH did not alter the inhibition potency, indicating that acetylshikonin is not a mechanism-based inhibitor. SKF-525A, a widely used non-specific P450 inhibitor, had no inhibitory activity against CYP1A2, 2A6, 2E1 and 2J2, while it showed an inhibitory effect against CYP2B6, CYP2C19 and 2D6 with IC50 values of 2.5, 3.6 and 0.5 μ m, respectively. Our findings indicate that acetylshikonin may be a novel general P450 inhibitor, which could replace SKF-525A.
- Shon, Jong Cheol,Phuc, Nguyen Minh,Kim, Won Cheol,Heo, Jae Kyung,Wu, Zhexue,Lee, Hyunyoung,Liu, Kwang-Hyeon
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p. 553 - 556
(2017/12/15)
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- Study of temperature dependent three component dynamic covalent assembly VIa Hantzsch reaction catalyzed by dioxido- and oxidoperoxidomolybdenum(VI) complexes under solvent free conditions
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Tridentate ONO donor ligands derived from heterocyclic compound 4-acetyl-3-methyl-1-phenyl-2-pyrazoline-5-one (Hap) and aromatic hydrazides {benzoyl hydrazide (Hbhz), isonicotinoyl hydrazide (Hinh), nicotinoyl hydrazide (Hnah) and furoyl hydrazide (Hfah)} react with [MoVIO2(acac)2] (Hacac = acetylacetone) in equimolar ratio in methanol to give dioxidomolybdenum(vi) complexes, [MoO2(ap-bhz)(MeOH)] 1, [MoO2(ap-inh)(MeOH)] 2, [MoO2(ap-nah)(MeOH)] 3 and [MoO2(ap-fah)(MeOH)] 4. Reaction of these ligands with in situ generated oxidoperoxidomolybdenum(vi) precursor results in the formation of oxidoperoxidomolybdenum(vi) complexes, [MoO(O2)(ap-bhz)(MeOH)] 5, MoO(O2)(ap-inh)(MeOH)] 6, MoO(O2)(ap-nah)(MeOH)] 7 and MoO(O2)(ap-fah)(MeOH)] 8. These complexes have been characterized by elemental analysis, spectroscopic techniques (infrared, UV-vis, 1H and 13C NMR) and thermogravemetric analysis. The structures of complexes [MoVIO2(ap-bhz)(H2O)] 1a (water coordinated), [MoVIO2(ap-bhz)(DMSO)] 1b (DMSO coordinated), [MoVIO2(ap-nah)(DMF)] 3a (DMF coordinated), [MoVIO(O2)(ap-bhz)(MeOH)] 5 (methanol coordinated) and [MoVIO(O2)(Hap-nah)(OMe)]·MeOH 7a (methoxy coordinated) have been confirmed by single crystal X-ray studies. X-ray diffraction study also reveals that tridentate ligands bind to the metal center through enolic oxygen (of pyrazolol), azomethine nitrogen and enolic oxygen (of hydrazide) atoms. In complex 7a, pyridinic nitrogen is protonated. These complexes [dioxidomolybdenum(vi) as well as oxidoperoxidomolybdenum(vi)] have been tested as catalysts for temperature dependent one pot three component (methylacetoacetate, benzaldehyde and ammonium acetate) dynamic covalent assembly, via Hantzsch reaction, using 30% H2O2 as a green oxidant under solvent free conditions. Various parameters such as the amount of catalyst, oxidant and temperature of the reaction mixture have been taken into consideration to optimize the reaction conditions. In the Hantzsch reaction, the temperature and oxidant control the conversion and selectivity of the desired product.
- Maurya, Mannar R.,Saini, Neeraj,Avecilla, Fernando
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p. 12993 - 13009
(2016/02/12)
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- Metal-free-mediated oxidation aromatization of 1,4-dihydropyridines to pyridines using visible light and air
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A metal-free and environmentally friendly aerobic aromatization photosensitized by organic dye eosin Y bis(tetrabutyl ammonium salt) (TBA-eosinY) has been developed. With the aid of K2CO3, the aerobic catalytic system converts 1,4-dihydropyridines to their corresponding pyridine derivatives efficiently under visible light irradiation (λ=450 nm) at room temperature.
- Wei, Xiaojing,Wang, Lin,Jia, Wenliang,Du, Shaofu,Wu, Lizhu,Liu, Qiang
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p. 1245 - 1250
(2015/02/05)
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- Structure-function analysis of porcine cytochrome P450 3A29 in the hydroxylation of T-2 toxin as revealed by docking and mutagenesis studies
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T-2 toxin, one of the type A trichothecenes, presents a potential hazard to human and animal health. Our previous work demonstrated that porcine cytochrome P450 3A29 (CYP3A29) played an important role in the hydroxylation of T-2 toxin. To identify amino a
- Cheng, Guyue,Liu, Changcun,Wang, Xu,Ma, Hongmin,Pan, Yuanhu,Huang, Lingli,Hao, Haihong,Dai, Menghong,Yuan, Zonghui
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- The protection of nifedipin from photodegradation due to complex formation with β-cyclodextrin
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The inclusion complex β-cyclodextrin:nifedipin was prepared in solid state by coprecipitation with 1:1 mol ratio. The structure of the obtained complex and nifedipin was characterized by use of X-ray diffraction (XR), infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and differential scanning calorimetry (DSC) methods. The photodegradation of nifedipin and the β-cyclodextrin:nifedipin inclusion complex in solid state was monitored under natural daylight by infrared spectroscopy, whereby the free nifedipin degraded four to five times faster than the complexed nifedipin. The photodegradation products of both free and complexed nifedipin, formed during irradiation at 350 nm (with corresponding energy flux of 18 W m-2) were monitored by liquid chromatography during various time intervals. The speed of formation of nitroso- and nitro-phenyl derivatives by nifedipin irradiation was significantly higher than those of complexed nifedipin irradiation, which indicates its increased photostability in the inclusion complex. The effect on this property is significant because it contributes both to the improvement of the therapeutic effect of nifedipin and to the safer application thereof.
- Nikolic, Vesna,Ilic, Dusica,Nikolic, Ljubisa,Stankovic, Mihajlo,Cakic, Milorad,Stanojevic, Ljiljana,Kapor, Anges,Popsavin, Mirjana
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body text
p. 744 - 749
(2011/11/14)
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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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- A highly efficient biomimetic aromatization of Hantzsch-1,4-dihydropyridines with t-butylhydroperoxide, catalysed by iron(III) phthalocyanine chloride
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Rapid aromatization of Hantzsch-1,4-DHPs with t-butylhydroperoxide catalysed by iron(III) phthalocyanine chloride is described. The reaction proceeds smoothly at room temperature within 1-35 min and the products of high purity were isolated in excellent yields. To explain the reactivity of this catalytical system plausible mechanism have been proposed to involve formation of high-valent oxoferryl species as in cytochrome P450 itself.
- Filipan-Litvic, Mirela,Litvic, Mladen,Vinkovic, Vladimir
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experimental part
p. 9276 - 9282
(2009/04/05)
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- An efficient, metal-free, room temperature aromatization of Hantzsch-1,4-dihydropyridines with urea-hydrogen peroxide adduct, catalyzed by molecular iodine
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A mild, highly efficient and metal-free synthetic method for aromatization of 1,4-dihydropyridines employing urea-hydrogen peroxide adduct as oxidant catalyzed by 20 mol % of molecular iodine was developed. The reaction was carried out in ethyl acetate at room temperature and the products were isolated in high to excellent yields. A plausible free-radical mechanism is proposed based on results obtained with derivatives having alkyl and aryl substituents in the 1,4-dihydropyridine ring.
- Filipan-Litvi?, Mirela,Litvi?, Mladen,Vinkovi?, Vladimir
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p. 5649 - 5656
(2008/09/21)
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- Oxidative aromatization of Hantzsch 1,4-dihydropyridines in the presence of mixed-addenda vanadomolybdophosphate heteropolyacid, H6PMo9V3O40
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A variety of Hantzsch 1,4-dihydropyridines were oxidized to the corresponding pyridines in high yields in the presence of H6PMo9V3O40, a Keggin type heteropolyacid, in refluxing acetic acid. The heteropolyacid w
- Heravi, Majid M.,Derikvand, Fatemeh,Hassan-Pour, Shahla,Bakhtiari, Khadijeh,Bamoharram, Fatemeh F.,Oskooie, Hossein A.
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p. 3305 - 3309
(2008/02/09)
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- Photochemistry of 4-(2-Nitrophenyl)-1,4-dihydropyridines. Evidence for electron transfer and formation of an intermediate
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New evidence about the path followed in the photochemical reaction of 4-(2-nitrophenyl)-1,4-dihydropyridines such as the drugs nifedipine (Compound 1) and nisoldipine (Compound 2) to give the corresponding nitrosophenylpyridines has been found through determination of the steady-state photochemical parameters and a comparison of the photoreactions in solution and in matrix at 90 K. Additional support is given by comparison with the isomeric 4-(3-nitrophenyl)dihydropyridine as well as with simpler derivatives, such as the corresponding 4-methyldihydropyridine. In Compounds 1 and 2, the lowest lying singlet, localized on the dihydropyridine chromophore, is deactivated by (largely exothermic) electron transfer to the nitrobenzene moiety, as evidenced by the complete quenching of the blue fluorescence observed in analogues not containing the electron-accepting group. Intramolecular proton transfer ensues in the 2-nitrophenyl derivatives with a relatively medium-independent quantum yield of ～0.3 and leads to an aromatic zwitterion, which is detected in matrix at 90 K (photoionization of this intermediate takes place in 2-methyltetrahydrofuran secondary). The intermediate is smoothly converted into the end product upon melting the glass. The 3-nitrophenyl analog, for which such a path is not available, is less reactive by about three orders of magnitude at 366 nm, although the quantum yield arrives at ～0.01 by irradiation at 254 nm in MeOH, reasonably via the nitrophenyl localized triplet.
- Fasani, Elisa,Dondi, Daniele,Ricci, Andrea,Albini, Angelo
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p. 225 - 230
(2008/02/09)
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- KBrO3/FeCl3 as an efficient oxidising system for aromatisation of Hantzsch 1,4-dihydropyridines in wet acetonitrile
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KBrO3 in the presence of anhydrous FeCl3 efficiently aromatised Hantzsch 1,4-dihydropyridines to their corresponding pyridine derivatives in high to excellent yields. The reactions were carried out in wet CH3CN under reflux condition.
- Zeynizadeh, Behzad,Dilmaghani, Karim Akbari,Roozijoy, Asli
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p. 657 - 658
(2007/10/03)
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- Aromatization of Hantzsch ester 1,4-dihydropyridines with iodine under normal conditions and ultrasound irradiation
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A variety of Hantzschester 1,4-dihydropyridines are efficiently oxidized to their corresponding pyridine compounds with iodine under normal conditions and ultra sound irradiation. There actions were carried out in refluxing CH 3CN.
- Zeynizadeh, Behzad,Dilmaghani, Karim Akbari,Roozijoy, Asli
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p. 1001 - 1004
(2007/10/03)
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- Oxidative-aromatization of Hantzsch ester 1,4-dihydropyridines by KBrO 3/SnCl4-5H2O under mild condition
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Different kinds of Hantzsch ester 1,4-dihydropyridines were oxidatively aromatized to their corresponding pyridine derivatives by KBrO 3/SnCl4 · 5H2O system in refluxing CH3CN. The products were obtained in high to excellent yields.
- Zeynizadeh, Behzad,Dilmaghani, Karim Akbari,Roozijoy, Asli
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p. 557 - 562
(2007/10/03)
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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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- 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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p. 2459 - 2468
(2007/10/03)
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- The oxidation of 4-alkyl and 4-aryl-1,4-dihydropyridines to pyridines with hydrogen peroxide in an ionic liquid
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An efficient oxidation of 4-alkyl and 4-aryl-1,4-dihydropyridines to the corresponding pyridines with hydrogen peroxide in ionic liquids at room temperature in excellent yields is described.
- Panchgalle, Sharad P.,Choudhary, Suman M.,Chavan, Subhash P.,Kalkote, Uttam R.
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p. 550 - 551
(2007/10/03)
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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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p. 1750 - 1757
(2007/10/03)
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- Formation of substituted 6-hydroxy-5-oxo-5,6-dihydrobenzo[c][2,7] naphthyridine upon photochemical transformation of nifedipine
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Long-term exposure of nifedipine to daylight in ethanol gives 2,2′-bis[3,5-bis(methoxycarbonyl)-2,6-dimethylpyridin-4-yl]azoxybenzene and 6-hydroxy-1-methoxycarbonyl-2,4-dimethyl-5-oxo-5,6-dihydrobenzo[c] [2,7]naphthyridine as the major products.
- Krivopalov,Sedova,Shkurko
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p. 2440 - 2443
(2007/10/03)
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- An efficient Co(II) catalyzed auto oxidation of 1,4-dihydropyridines
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An efficient Co(II) catalyzed auto oxidation of 1,4-dihydropyridines to pyridines in good to excellent yield is described.
- Chavan, Subhash P.,Kharul, Rajendra K.,Kalkote, Uttam R.,Shivakumar
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p. 1333 - 1340
(2007/10/03)
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- Iron and transition metal transport into erythrocytes mediated by nifedipine degradation products and related compounds
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The aim of this investigation was to determine the mechanism of action of the nitrosophenylpyridine derivative of nifedipine ("nitrosonifedipine", NN) on Fe(II) transport into erythrocytes. Nifedipine is rapidly degraded to NN by daylight. We used rabbit erythrocytes, NN, and several chemically related substances, and examined their effects on the transfer of iron and other transition metals (cadmium, cobalt, manganese, nickel, zinc) into and out of the cells. NN mediated the transfer of iron and zinc but not the other metals into the cell cytosol. The transfer of Fe(II) was not affected by changes in cell membrane potential and could not be ascribed to free radical production. Two hydroxamic acid compounds chemically related to NN also stimulated iron and zinc uptake, but no evidence was obtained for cell-induced transformation of NN to them. In vivo, NN is probably converted to a lactam derivative. This compound was found to have no effect on iron uptake by the cells. It is concluded that NN has a relatively high specificity for the transport of iron compared with other transition metals, and small changes in its structure markedly affect this action. Also, because the lactam to which NN is converted in vivo is inactive, it is unlikely that nifedipine will affect iron metabolism after therapeutic administration.
- Savigni, Donna L.,Wege, Dieter,Cliff, Garth S.,Meesters, Mark L.H.,Morgan, Evan H.
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p. 1215 - 1226
(2007/10/03)
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- Silica gel supported chromium trioxide: An effective reagent for aromatization of 4-alkyl/aryl-1,4-dihydropyridines
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Oxidation of 4-alkyl/aryl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid diesters 1 has been carried out using silica gel supported CrO3 reagent. The supported reagent is prepared by co-grinding, CrO3 with silica gel in an agate mortar. In all the cases the corresponding aromatized product 2 is obtained in excellent yields (75-95 percent). Dealkylated product 3 obtained during oxidation of 4-isopropyl-1,4-dihydropyridine.
- Khadilkar, Bhushan,Jaisinghani, Harsha,Khare, Atul
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p. 817 - 818
(2007/10/03)
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- An efficient oxidation of 1,4-dihydropyridines using aqueous tert.- Butylhydroperoxide
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Aromatization of 4-substituted 1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate using aqueous tert.-butylhydroperoxide in 74-87% yield has been achieved.
- Chavan, Subhash P.,Dantale, Shubhada W.,Kalkote, Uttam R.,Jyothirmai,Kharul, Rajendra K.
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p. 2789 - 2792
(2007/10/03)
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- Newly discovered photodegradation products of nifedipine in hospital prescriptions
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New photodegradation products of nifedipine (1) have been isolated. They were found in tablets dispensed in the pulverized form by hospitals. 1 decomposed concurrently into six components after storage of 30 days under exposure to normal room light. The main photoproduct was a nitroso derivative (2) and others were minor. Preparative thin-layer chromatography has been used to isolate the six photodegradation products. The chemical structures of these isolated compounds were identified or estimated by comparison with authentic samples and/or using UV, IR, 1H NMR, mass spectroscopy, melting point determination, and elementary analysis. From these analyses, it was found that 1 was converted into a cis-azoxy derivative (4), a trans-azoxy derivative (5), a N,N'-dioxide derivative (6) and a lactam derivative (7) in addition to 2 and a nitro derivative (3). Furthermore, it is proposed that 2 is mainly responsible for the formation of these new products (4-7) by photochemical condensation.
- Hayase,Itagaki,Ogawa,Akutsu,Inagaki,Abiko
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p. 532 - 538
(2007/10/02)
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- Kinetic analysis of nifedipine photodegradation in the solid state
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Photodegradation of nifedipine (1) was studied using the accelerated test which involves irradiation of 1 compressed into a KBr tablet with UV light of λ = 254 nm. It was found that 1 photodegradation in the solid state is a simple, one-step first order reaction of the A → B type, yielding nitroso derivative (95%) and trace amounts of two other compounds. The rate of the process is inversely proportional to the thickness of the irradiated layer and to the initial concentration. It does not depend on the degree of refinement. The mechanism of 1 photodegradation in the solid and liquid state is identical, the only difference is the rate of the process: in the solid state it is 15 to 20 times slower.
- Marciniec,Rychcik
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p. 894 - 897
(2007/10/02)
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- EFFECT OF NIFEDIPINE ON ALKALOID ACCUMULATION IN CATHARANTHUS ROSEUS CELL CULTURES
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The effect of nifedipine on both alkaloid accumulation and calcium uptake in Catharanthus roseus cell cultures was investigated.It was shown that nifedipine inhibited ajmalicine accumulation through a mechanism other than blocking of the calcium channel u
- Merillon, J. M.,Liu, D.,Laurent, Y.,Rideau, M.,Viel, C.
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p. 1609 - 1612
(2007/10/02)
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- Synthesis of spin-labelled 1,4-dihydropyridines and pyridines
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1,4-Dihydropyridines spin-labelled with 5- and 6-membered nitroxyl radicals in positions 1-4 of the pyridine ring were synthesized. The oxidation of these dihydropyridines to pyridines with active manganese dioxide was investigated.
- Hankovszky,Sar,Hideg,Jerkovich
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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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