5521-55-1Relevant articles and documents
Hederagenin compound H-X with anti-lung cancer effect and preparation method and application thereof
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Paragraph 0048; 0049; 0051; 0052; 0120; 0121, (2020/04/17)
The invention provides a hederagenin compound H-X with an anti-tumor effect and a preparation method and application thereof. The structural general formula 1 is shown in the specifications. Most of the derivatives provided by the invention have obvious inhibition effects on tumor cells A549, MCF-7 and HepG2, and the compound hederagenin-2, 6-dimethylpyrazine (H-08) shows good selectivity betweentumors and normal conditions, especially on lung cancer A549 cells. The IC50 of the compound to A549, MCF-7, HepG2, MDCK and H9c2 is 3.45+/-0.59 muM, 8.73+/-1.49 muM, 8.71+/-0.38 muM, 14.11+/-0.04 muM, and 16.69+/-0.12 muM, the inhibition effect on A549 cells is similar to that of a positive drug cis-platinum (IC50 is 3.85+/-0.63 muM), but the toxicity on MDCK and H9c2 is obviously lower than thatof cis-platinum.
Method for preparing 5-methylpyrazine-2-carboxylic acid by catalytic oxidation
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Paragraph 0023-0032, (2019/03/08)
The invention discloses a method for preparing 5-methylpyrazine-2-carboxylic acid by catalytic oxidation. According to the invention, Mn-W-Co/diatomite is used as a catalyst, 2,5-dimethylpyrazine is used as a raw material, oxygen is used as an oxidant, and 5-methylpyrazine-2-carboxylic acid is synthesized by catalytic oxidation. The method comprises the following steps: packing Mn-W-Co/diatomite catalyst into a fixed bed reactor with temperature of 200-400 DEG C, introducing the reaction raw material 2,5-dimethylpyrazine into a reaction tube of the fixed bed reactor packed with Mn-W-Co/diatomite supported catalyst by bubbling with high temperature water vapor, introducing oxygen separately into the reaction tube, carrying out catalytic oxidation of 2,5-dimethylpyrazine in the catalyst bedto produce 5-methylpyrazine-2carboxylic acid, carrying the product out of the reaction tube by water vapor, condensing, crystallizing, and collecting. In the invention, the preparation method of the Mn-W-Co/diatomite catalyst is simple. The method for preparing 5-methylpyrazine-2carboxylic acid by continuous catalytic oxidation in the fixed bed is environmentally friendly, pollution-free, simple in operation, easy in control, high in 5-methylpyrazine-2-carboxylic acid yield and easy in industrial production.
Synthesis process of 2-methyl-5-pyrazinecarboxylic acid
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, (2019/03/08)
The invention provides a method for preparing 2-methyl-5-pyrazinecarboxylic acid. The method provided by the invention is characterized in that potassium permanganate which is more harmful to the environment is not used, a target compound 2-methyl-5-pyrazinecarboxylic acid can be prepared from cheap and easily available methylglyoxal and 2-amino malonamide taken as raw materials through four stepsof cyclization, hydrolysis, chlorination and reduction, the yield of the reaction route is high, the amount of byproducts is small, and products are purer.
Method for preparing 5-methylpyrazine-2-carboxylic acid
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Paragraph 0016; 0022-0025, (2018/06/20)
The invention relates to a method for preparing 5-methylpyrazine-2-carboxylic acid. The preparation method comprises that 2, 5-dimethylpyrazine as a raw material undergoes a monomethyl oxidation reaction in an aqueous solution under control of amounts of 2, 5-dimethylpyrazine and potassium permanganate, the product is subjected to suction filtration, the filtrate is concentrated, the pH of the concentrate is adjusted, the concentrate is extracted, the extract is concentrated, is decolored through activated carbon and is hot-filtered, the filtrate is cooled to form crystals, and the crystals are subjected to suction filtration and then are dried so that 5-methylpyrazine-2-carboxylic acid is obtained. The preparation method can effectively reduce the occurrence of the side oxidization reaction of two methyl groups on the raw material 2, 5-dimethylpyrazine at the same time, and the product yield is 75% or more. In the post-treatment, the pH value of the system is adjusted, the conversionof the by-product potassium pyrazine dicarboxylate is controlled, the product purity is 99.5% and industrial production is realized.
Design, synthesis, and cytotoxic analysis of novel hederagenin–pyrazine derivatives based on partial least squares discriminant analysis
Fang, Kang,Zhang, Xiao-Hua,Han, Yao-Tian,Wu, Gao-Rong,Cai, De-Sheng,Xue, Nan-Nan,Guo, Wen-Bo,Yang, Yu-Qin,Chen, Meng,Zhang, Xin-Yu,Wang, Hui,Ma, Tao,Wang, Peng-Long,Lei, Hai-Min
, (2018/10/20)
Hederagenin (He) is a novel triterpene template for the development of new antitumor compounds. In this study, 26 new He–pyrazine derivatives were synthetized in an attempt to develop potent antitumor agents; they were screened for in vitro cytotoxicity against tumor and non-tumor cell lines. The majority of these derivatives showed much stronger cytotoxic activity than He. Remarkably, the most potent was compound 9 (half maximal inhibitory concentration (IC50) was 3.45 ± 0.59 μM), which exhibited similar antitumor activities against A549 (human non-small-cell lung cancer) as the positive drug cisplatin (DDP; IC50 was 3.85 ± 0.63 μM), while it showed lower cytotoxicity on H9c2 (murine heart myoblast; IC50 was 16.69 ± 0.12 μM) cell lines. Compound 9 could induce the early apoptosis and evoke cell-cycle arrest at the synthesis (S) phase of A549 cells. Impressively, we innovatively introduced the method of cluster analysis modeled as partial least squares discriminant analysis (PLS-DA) into the structure–activity relationship (SAR) evaluation, and SAR confirmed that pyrazine had a profound effect on the antitumor activity of He. The present studies highlight the importance of pyrazine derivatives of He in the discovery and development of novel antitumor agents.
A 5-methylpyrazine-2-carboxylic acid
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Paragraph 0035; 0036, (2017/03/08)
The invention discloses a preparation method of 5-methylpyrazine-2-carboxylic acid, and relates to the technical field of preparation of a heterocyclic compound on which 3 bonds are connected to heteroatoms and an ester group is directly connected to a cyclic carbon atom. The preparation method comprises the steps of in a normal pressure fixed bed reactor, diluting 2,5-dimethylpyrazine which is taken as a raw material, introducing normal pressure air, oxidizing in the presence of a catalyst at the the temperature of 150-350 DEG C to obtain 5-methylpyrazine-2-carboxylic acid, wherein the catalyst consists of a carrier and active components; the carrier is gamma-Al2O3, and the active components are one or more of metallic oxides of Mn, V, Ti and Sr; each active component accounts for 1-20%, and the total active component accounts for 5-30% in terms of total mass of the catalyst. According to the invention, used catalyst is simple to prepare and stable in avidity; the method is easy to control in operation condition, short in reaction step, high in yield, free from pollution and applicable to industrial production.
Recurrence of carboxylic acid-pyridine supramolecular synthon in the crystal structures of some pyrazinecarboxylic acids
Vishweshwar, Peddy,Nangia, Ashwini,Lynch, Vincent M.
, p. 556 - 565 (2007/10/03)
X-ray crystal structures of pyrazinic acid 1 and isomeric methylpyrazine carboxylic acids 2-4 are analyzed to examine the occurrence of carboxylic acid-pyridine supramolecular synthon V in these heterocyclic acids. Synthon V, assembled by (carboxyl)O-H···N(pyridine) and (pyridine)C-H···O(carbonyl) hydrogen bonds, controls self-assembly in the crystal structures of pyridine and pyrazine monocarboxylic acids. The recurrence of acid-pyridine heterodimer V compared to the more common acid-acid homodimer I in the crystal structures of pyridine and pyrazine monocarboxylic acids is explained by energy computations in the RHF 6-31G* basis set. Both the O-H···N and the C-H···O hydrogen bonds in synthon V result from activated acidic donor and basic acceptor atoms in 1-4. Pyrazine 2,3- and 2,5-dicarboxylic acids 10 and 11 crystallize as dihydrates with a (carboxyl)O-H···O(water) hydrogen bond in synthon VII, a recurring pattern in the diacid structures. In summary, the carboxylic acid group forms an O-H···N hydrogen bond in pyrazine monocarboxylic acids and an O-H···O hydrogen bond in pyrazine dicarboxylic acids. This structural analysis correlates molecular features with supramolecular synthons in pyridine and pyrazine carboxylic acids for future crystal engineering strategies.
Hydrolytic and metabolic characteristics of the esters of 1-(3'- hydroxypropyl)-2-methyl-3-hydroxypyridin-4-one (CP41), potentially useful iron chelators
Liu, Ding Y.,Liu, Zu D.,Lu, Shu L.,Hider, Robert C.
, p. 228 - 233 (2007/10/03)
1-(3'-Hydroxypropyl)-2-methyl-3-hydroxypyridin-4-one (CP41) has been extensively investigated as an orally effective iron chelator. In order to improve the pharmacokinetic and metabolic properties of CP41, eleven aromatic esters have been synthesized and tested as potential prodrugs. In the present study, the hydrolytic rates of these CP41 esters in phosphate buffer (pH2.0 and pH7.4), rat blood and rat liver homogenate have been determined and found to cover a wide range. Generally, they possessed relatively slow hydrolytic rates in phosphate buffer (0-50 nmol/ml/hr at pH 2.0 and 0-140 nmol/ml/hr at pH 7.4). The hydrolytic rates in rat blood fell in the range of 9-5766 nmol/ml blood/hr and in rat liver homogenate 1-800 μmol/g liver tissue/hr. All esters possess a higher lipophilicity than that of the parent compound CP41. Although no apparent relationship was observed between the lipophilicities and hydrolytic rates, the esters with relatively higher hydrolytic rates in liver homogenate tend to possess higher iron scavenging efficacies. Further investigation of the metabolism of selected CP41 esters indicates that metabolism is a key factor influencing the efficacy of CP41 esters, as some esters can be metabolically inactivated in the liver in preference to undergoing ester hydrolysis. Ester design, combined with a knowledge of the prodrug metabolism, is a useful strategy for the production of 3-hydroxypyridin-4-ones with enhanced iron scavenging efficacy.
ANODIC OXIDATION OF METHYL-SUBSTITUTED NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS AT THE ACTIVATED NICKEL OXIDE ELECTRODE
Feldman, D.,Chervenka, M.,Stokh, E.,Shimanska, M.,Khaber, E.
, p. 80 - 85 (2007/10/03)
Methyl derivatives of several nitrogen-containing heterocyclic compounds were converted into the corresponding carboxylic acids by means of electrochemical oxidation at the nickel oxohydroxide anode in alkaline medium, using a nondiaphragm electrolyzer.The oxidation of 2,5-dimethylpyrazine was used to demonstrate the effect of adding chromium (III) and cobalt (II) compounds to the reaction mixture.The composition and electronic state of the anode surface were studied using x-ray diffraction and XPS methods.
