![2-[2-(phthalimido)ethoxymethyl]-3-ethoxycarbonyl-4-(o-chlorophenyl)-5-methoxycarbonyl-6-methylpyridine](/Databaselist/images/loading.webp)
113994-41-5Relevant academic research and scientific papers
A simple sonochemical assisted synthesis of NiMoO4/chitosan nanocomposite for electrochemical sensing of amlodipine in pharmaceutical and serum samples
Lou, Bih-Show,Rajaji, Umamaheswari,Chen, Shen-Ming,Chen, Tse-Wei
, (2020)
In this investigation, a facile sonochemical route has been developed for the preparation of porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO4/CHIT) by using ammonium molybdate and nickel(II) acetate tetrahydrate and as nickel and molybdate precursor, respectively (ultrasonic power 60 W/cm2 and frequency 20 kHz). The ultrasonic based materials preparation as a fast, convenient and economical approach has been widely used to generate novel nanomaterials. Herein, we report an efficient voltammetric sensor for amlodipine drug by using porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO4/CHIT). Its structure and properties were characterized by x-ray diffraction pattern, scanning electron microscope, transmission electron microscope, elemental analysis and mapping. The electrochemical studies are indicated the NiMoO4/CHIT modified glassy carbon electrode (GCE) exhibited the good performance towards electrocatalytic sensing of amlodipine drug. Consequently, a linear correlation between the anodic peak current with sensor concentration 0.025–373.6 μM with a detection limit and sensitivity of 4.62 nM and 4.753 μA·μM?1·cm?2, respectively. A voltammetry based drug analysis was found to be high sensitive and reproducible, which able to detect nanomolar concentration. Furthermore, the fabricated electrochemical sensor was applied in drug and biological samples.
Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation
Zhu, Yanlin,Wang, Fen,Li, Quan,Zhu, Mingshe,Du, Alicia,Tang, Wei,Chen, Weiqing
, p. 245 - 249 (2014)
Amlodipine is a commonly prescribed calcium channel blocker for the treatment of hypertension and ischemic heart disease. The drug is slowly cleared in humans primarily via dehydrogenation of its dihydropyridine moiety to a pyridine derivative (M9). Results from clinical drug-drug interaction studies suggest that CYP3A4/5 mediate metabolism of amlodipine. However, attempts to identify a role of CYP3A5 in amlodipine metabolism in humans based on its pharmacokinetic differences between CYP3A5 expressers and nonexpressers failed. Objectives of this study were to determine the metabolite profile of amlodipine (a racemic mixture and S-isomer) in human liver microsomes (HLM), and to identify the cytochrome P450 (P450) enzyme(s) involved in the M9 formation. Liquid chromatography/mass spectrometry analysis showed that amlodipine was mainly converted to M9 in HLM incubation. M9 underwent further O-demethylation, O-dealkylation, and oxidative deamination to various pyridine derivatives. This observation is consistent with amlodipine metabolism in humans. Incubations of amlodipine with HLM in the presence of selective P450 inhibitors showed that both ketoconazole (an inhibitor of CYP3A4/5) and CYP3cide (an inhibitor of CYP3A4) completely blocked the M9 formation, whereas chemical inhibitors of other P450 enzymes had little effect. Furthermore, metabolism of amlodipine in expressed human P450 enzymes showed that only CYP3A4 had significant activity in amlodipine dehydrogenation. Metabolite profiles and P450 reaction phenotyping data of a racemic mixture and S-isomer of amlodipine were very similar. The results from this study suggest that CYP3A4, rather than CYP3A5, plays a key role in metabolic clearance of amlodipine in humans. Copyright
Measurement of Intracellular Nitric Oxide with a Quantitative Mass Spectrometry Probe Approach
Zhong, Zhu-Jun,Yao, Zhong-Ping,Shi, Zi-Qi,Liu, Yang-Dan,Liu, Li-Fang,Xin, Gui-Zhong
, p. 8536 - 8543 (2021)
Nitric oxide (NO) is a molecule of physiological importance, and the function of NO depends on its concentration in biological systems, particularly in cells. Concentration-based analysis of intracellular NO can provide insight into its precise role in health and disease. However, current methods for detecting intracellular NO are still inadequate for quantitative analysis. In this study, we report a quantitative mass spectrometry probe approach to measure NO levels in cells. The probe, Amlodipine (AML), comprises a Hantzsch ester group that reacts with NO to form a pyridine, Dehydro Amlodipine (DAM). Quantification of DAM by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) allows specific measurement of intracellular NO levels. Notably, the AML/NO reaction proceeds rapidly (within 1 s), which is favorable for NO detection considering its large diffusivity and short half-life. Meanwhile, studies under simulated physiological conditions revealed that the AML response to NO is proportional and selective. The presented UPLC-MS/MS method showed high sensitivity (LLOQ = 0.24 nM) and low matrix interference (less than 15%) in DAM quantification. Furthermore, the mass spectrometry probe approach was demonstrated by enabling the measurement of endogenous and exogenous NO in cells. Hence, the quantitative UPLC-MS/MS method developed using AML as a probe is expected to be a new method for intracellular NO analysis.
Method for preparing levamlodipine
-
Paragraph 0044-0056, (2020/10/14)
The invention provides a method for preparing levamlodipine and belongs to the technical field of medicine synthesis. The method provided by the invention comprises the following steps: concentratingamlodipine resolution mother liquor to be dry, then mixing with an oxidizing agent and a first solvent, and carrying out an oxidation reaction to obtain 2-((2-aminoethoxy)methyl)-4-(2-chlorphenyl)-6-methyl-3,5-pyridine ethyl methyl diformate, wherein the oxidizing agent is an achiral reagent; mixing the 2-((2-aminoethoxy)methyl)-4-(2-chlorphenyl)-6-methyl-3,5-pyridine ethyl methyl diformate, a reducing agent and a second solvent, and carrying out a reduction reaction to obtain an amlodipine racemate; and mixing the amlodipine racemate, a resolution reagent and a third solvent, and carrying outresolution treatment to obtain levamlodipine. According to the method provided by the invention, the amlodipine in the amlodipine resolution mother liquor can be effectively recycled and converted into high-value levamlodipine.
Dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection (by machine translation)
-
Paragraph 0047-0054, (2019/01/08)
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)
EX VIVO METHODS FOR PREDICTING AND CONFIRMING IN VIVO METABOLISM OF PHARMACEUTICALLY ACTIVE COMPOUNDS
-
Page/Page column 38; 39; 40, (2015/06/25)
Methods and compositions for the catalytic oxidation of pharmaceutically active compounds, and more particularly to ex vivo methods for predicting in vivo metabolism of pharmaceutically active compounds, including predicting in vivo interaction between two or more pharmaceutically active compounds.
Phototransformation of Amlodipine: Degradation Kinetics and Identification of Its Photoproducts
Jakimska, Anna,?liwka-Kaszyńska, Magdalena,Nagórski, Piotr,Namies?nik, Jacek,Kot-Wasik, Agata
, (2016/03/12)
Nowadays, monitoring focuses on the primary compounds and does not include degradation products formed during various biological and chemical processes. Transformation products may have the same effects to human health and the environment or sometimes they can be more toxic than the parent compound. Unfortunately, knowledge about the formation of degradation products is still limited, however, can be very important for the environmental risk assessment. Firstly, the photodegradation kinetic of amlodipine was investigated in two experimental conditions: during the exposure to solar radiation and during the exposure to the light emitted by the xenon lamp. In all cases degradation of amlodipine followed a pseudo-first-order kinetics. In the next step, identification of transformation products of amlodipine formed during the exposure to xenon lamp irradiation was performed using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). As a result sixteen photoproducts were identified, their structures were elucidated and ultimately the transformation pathway was proposed. Fifteen compounds (out of 16 photoproducts) were newly identified and reported here for the first time; some of those compounds were formed from the first photoproduct, amlodipine pyridine derivative. Several analytes were formed only in acidic or basic conditions. Furthermore, the occurrence of amlodipine and its identified degradation products was investigated in environmental waters. Only one out of 16 compounds was found in wastewater effluent. The possibility of the sorption of examined analytes to sewage sludge particles was discussed based on QSAR.
Study on the oxidation of C4-phenolic-1,4-dihydropyridines and its reactivity towards superoxide radical anion in dimethylsulfoxide
Salazar, Ricardo,Navarrete-Encina,Squella,Barrientos,Pardo-Jiménez,Nú?ez-Vergara, Luis J.
experimental part, p. 841 - 852 (2011/03/22)
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.
Reactivity of C4-indolyl substituted 1,4-dihydropyridines toward superoxide anion (O2O) in dimethylsulfoxide
Salazar, Ricardo,Navarrete-Encina,Squella,Camargo,Nunez-Vergara, Luis J.
scheme or table, p. 569 - 577 (2010/07/02)
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.
Mild, selective, and high-yield oxidation of hantzsch 1,4-dihydropyridines with lead(IV) acetate
Litvic, Mladen,Cepanec, Ivica,Filipan, Mirela,Kos, Karmen,Bartolincic, Anamarija,Druskovic, Vinka,Tibi, Mohamed Majed,Vinkovic, Vladimir
, p. 23 - 35 (2007/10/03)
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.
