Journal of Organic and Pharmaceutical Chemistry最新文献

Obtaining the Enoxaparin Sodium Substance Equivalent to the Original Clexane® and Lovenox®. The Selection of Technological Parameters and Optimization of the “Greenness” of the Purification Stage 获得与 Clexane® 和 Lovenox® 原药等效的依诺肝素钠物质。技术参数的选择和纯化阶段 "绿色 "的优化

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-11-07 DOI: 10.24959/ophcj.23.290670

Yuliia Bovsunovska, V. Rudiuk, Nataliia Harna, Olha S. Holovchenko, V. Georgiyants

{"title":"Obtaining the Enoxaparin Sodium Substance Equivalent to the Original Clexane® and Lovenox®. The Selection of Technological Parameters and Optimization of the “Greenness” of the Purification Stage","authors":"Yuliia Bovsunovska, V. Rudiuk, Nataliia Harna, Olha S. Holovchenko, V. Georgiyants","doi":"10.24959/ophcj.23.290670","DOIUrl":"https://doi.org/10.24959/ophcj.23.290670","url":null,"abstract":"The aim of the study was to adjust and optimize the purification stage of crude enoxaparin sodium to obtain a substance equivalent to the original drugs Clexane® and Lovenox® according to the criteria specified by the FDA. The purification stage involves the reprecipitation of crude enoxaparin in methanol. Determining the ratio of solvents required for the reprecipitation is important for studying the correlation between the experimental conditions of the technological process and the structural characteristics of enoxaparin samples. In the study, the method of purification of enoxaparin sodium described in the patent was assessed, and the following variations of the MeOH:H2O solvent ratio were selected – 4:1; 2:1; 1:1. The obtained samples of enoxaparin sodium were analyzed according to the in-house specification developed on the basis of the pharmacopoeial monograph, as well as by non-pharmacopoeial methods, such as two-dimensional NMR spectroscopy (HSQC) and size exclusion chromatography (SEC) for detailed characterization of the molecule. Strategies of greening of the enoxaparin sodium purification stage by reducing the E-factor were also considered in the study. Considering the principles of “green” chemistry, the method of purification of crude enoxaparin sodium was optimized by the solvent regeneration. It was experimentally possible to demonstrate the effect of the solvent ratio at the stage of purification of crude enoxaparin on the composition, as well as on the number and distribution of oligosaccharide fractions in the molecule. Based on the results of the study, it can be concluded that the ratio of MeOH:H2O=1:1 allows obtaining samples that are closest to Clexane® and Lovenox® in terms of the molecular weight distribution profile and the composition profile. The E-factor was also reduced from 14 to 5.25 by solvent regeneration.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139284824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New Method for Studying the Kinetics of the Release of Poorly Soluble API from Solid Oral Dosage Forms on the Example of Quertin® 以 Quertin® 为例研究固体口服剂型中难溶性原料药释放动力学的新方法

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-11-07 DOI: 10.24959/ophcj.23.290665

Nataliia V. Khanina, V. Georgiyants, V. Khanin, Igor A. Zupanetz

{"title":"A New Method for Studying the Kinetics of the Release of Poorly Soluble API from Solid Oral Dosage Forms on the Example of Quertin®","authors":"Nataliia V. Khanina, V. Georgiyants, V. Khanin, Igor A. Zupanetz","doi":"10.24959/ophcj.23.290665","DOIUrl":"https://doi.org/10.24959/ophcj.23.290665","url":null,"abstract":"In this paper, it is proposed to consider a new method developed for studying the kinetics of release of substances that are poorly soluble in aqueous media on the example of quercetin. The study object was the drug containing plant bioactive components – Quertin® chewable tablets, 40 mg, 3 blisters, 10 pcs – produced by PJSC SIC “Borshchahivskiy CPP”. An Agilent 1290 Infinity II LC System liquid chromatograph with an Agilent 6530 mass selective detector (Agilent Technologies) was used for the analysis. Solubility profiles were studied in accordance with the requirements of the Biopharmaceutical Classification System (BCS). The solubility limit of the substance in the media studied has been determined. A method for the quantitative determination of quercetin in test media in the range of specified concentrations with high sensitivity and selectivity has been developed. The dissolution of Quertin® chewable tablets in 3 different aqueous dissolution media with pH 1.2, pH 4.5 and pH 6.8 was studied, the dissolution profiles were compared, and the f2 factor was calculated. This factor is a criterion for evaluating the study by comparing dissolution kinetics with in vivo results. The results obtained indicate that the approach proposed to studying the kinetics of the release of substances that are sparingly soluble in aqueous solutions allows us to correctly assess the release of such substances in accordance with the requirements of the BCS. The method developed has been validated.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139287725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metrological Characteristics of the Potentiometric Assay Developed for Determining the Antioxidant Activity of Ascorbic Acid 为测定抗坏血酸抗氧化活性而开发的电位测定法的计量特性

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-10-28 DOI: 10.24959/ophcj.23.276394

O. Maslov, Sergii Kolisnyk, M. Komisarenko, E. Akhmedov, Alla O. Koval, T. A. Kostina, O. Kolisnyk

引用次数: 0

The Synthesis of Novel 2-Hetarylthiazoles via the Stille Reaction 通过 Stille 反应合成新型 2-专有噻唑

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-10-19 DOI: 10.24959/ophcj.23.288204

Dmytro O. Tarasenko, V. M. Kotliar

引用次数: 0

The Synthesis of Diverse Annulated Pyridines with 6-Membered Functionalized Saturated Cycles for Medical Chemistry Research 为医学化学研究合成具有 6 个功能饱和环的多种环状吡啶

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-10-19 DOI: 10.24959/ophcj.23.289263

Dmytro V. Yehorov, A. Subota

引用次数: 0

Features of Nitration of Aromatic Aldehydes with the Difluoromethoxy Group 芳香醛与二氟甲氧基的硝化特性

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-09-05 DOI: 10.24959/ophcj.23.285469

K. I. Petko, A. A. Filatov, T. M. Sokolenko

引用次数: 0

Incorporation of gem-Difluorocycloalkyl Substituents into Heterocycles via the Levin’s “Nitrogen Deletion” Strategy 通过Levin的“氮缺失”策略将宝石-二氟环烷基取代基纳入杂环

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-09-05 DOI: 10.24959/ophcj.23.278321

Serhii M. Holovach, Kostiantyn P. Melnykov, Maryna S. Poluektova, Oleksandr B. Rozhenko, O. Grygorenko

{"title":"Incorporation of gem-Difluorocycloalkyl Substituents into Heterocycles via the Levin’s “Nitrogen Deletion” Strategy","authors":"Serhii M. Holovach, Kostiantyn P. Melnykov, Maryna S. Poluektova, Oleksandr B. Rozhenko, O. Grygorenko","doi":"10.24959/ophcj.23.278321","DOIUrl":"https://doi.org/10.24959/ophcj.23.278321","url":null,"abstract":"A series of compounds containing heterocyclic cores and gem-difluorocycloalkyl substituents was obtained under conditions of the parallel synthesis (i.e., simultaneous performance of reaction procedures, treatment of the reaction mixture, and product isolation for a number of similar transformations) using the reductive amination – the “Nitrogen deletion” reaction sequence. The synthesis of the target compounds commenced from heteroaromatic aldehydes and the corresponding gem-difluorocycloalkyl or (gem-difluorocycloalkyl)methyl amines and included the NaBH3CN-mediated reductive amination and “Nitrogen deletion” upon the action of Levin’s anomeric amide. It has been shown that the method can be used to obtain compounds with the aforementioned structural fragments separated by one or two methylene units. The developed protocol allowed for the preparation of a 12-member compound library (67 % synthetic efficiency). Therefore, this novel synthetic methodology is suitable for decorating heterocyclic cores with sp3-enriched substituents that are attractive for medicinal chemistry.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82270022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of functionalized 4,5-dihydroisoxazoles decorated with the dimethylphosphinoyl group 二甲基膦酰基修饰的功能化4,5-二氢异恶唑的合成

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-08-21 DOI: 10.24959/ophcj.23.283988

Andrii V. Fedyk, B. Chalyk

{"title":"Synthesis of functionalized 4,5-dihydroisoxazoles decorated with the dimethylphosphinoyl group","authors":"Andrii V. Fedyk, B. Chalyk","doi":"10.24959/ophcj.23.283988","DOIUrl":"https://doi.org/10.24959/ophcj.23.283988","url":null,"abstract":"Aim. To synthesize a hybrid molecular platform incorporating dimethylphosphinoyl and 4,5-dihydroisoxazole moieties suitable for the creation of focused combinatorial libraries of compounds.Results and discussion. The base-promoted interaction of halogenoxides with dimethyl(vinyl)phosphine oxide under mild conditions allowed us to obtain 11 isoxazoline–dimethylphosphine oxide hybrids in moderate yields. The reaction was found to be regio- though non-stereoselective. Furoxans were identified as possible side products of the reaction.Experimental part. The one-pot interaction with dimethyl(vinyl)phosphine oxide was used for the synthesis of the target compounds. Nitrile oxides were obtained in situ from the corresponding halogenoximes by base-promoted generation. The ADME parameters for a synthesized 5-P(O)Me2-isoxazoline compared to its isosters with the same core structure were predicted using a SwissADME Web Tool. The compounds obtained were characterized by 1H, 13C, 19F, 31P NMR spectroscopy and HPLC-MS spectrometry methods, as well as the elemental analysis.Conclusions. A practical approach to the isoxazoline platform decorated with a 5-P(O)Me2 “magic” group and containing 3-substituent with an easy-to-modify functionality has been developed. On example of the piperidine derivative, the effect of the dimethylphosphinoyl group on physicochemical properties and ADME parameters compared to its isosters has been determined.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"195 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75888430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electrophilic Reactions of 7-(Trifluoromethyl)-2,3-dihydro- 1H-pyrrolizine: a Way Towards New Building Blocks 7-(三氟甲基)-2,3-二氢- 1h -吡咯利嗪的亲电反应:一种新的构建单元的方法

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-08-21 DOI: 10.24959/ophcj.23.284640

Anton A. Klipkov, I. Gerus

引用次数: 0

The Synthesis of the Hydrogenated Thiophenes by [3+2] Cycloaddition Reaction of Thiocarbonyl Ylide 硫代羰基醚[3+2]环加成反应合成氢化噻吩

Journal of Organic and Pharmaceutical Chemistry Pub Date : 2023-08-21 DOI: 10.24959/ophcj.23.283517

Tymofii V. Rudenko, V. Timoshenko

{"title":"The Synthesis of the Hydrogenated Thiophenes by [3+2] Cycloaddition Reaction of Thiocarbonyl Ylide","authors":"Tymofii V. Rudenko, V. Timoshenko","doi":"10.24959/ophcj.23.283517","DOIUrl":"https://doi.org/10.24959/ophcj.23.283517","url":null,"abstract":"Aim. To study the use of chloromethyl trimethylsilylmethyl sulfide as a precursor of thiocarbonyl ylide in [3+2] cycloaddition reaction to a number of α,β-unsaturated compounds and to establish the regularities of the reaction course. To develop an effective method for the synthesis of new dihydro- and tetrahydrothiophene derivatives which are convenient for further modification.Results and discussion. The synthetic approach to tetrahydrothiophenes with substituents in positions 3 and 4 was extended by the [3+2] cycloaddition reaction of thiocarbonyl ylide with a number of compounds containing an activated multiple bond. The stereoselectivity and limitations of this reaction were determined. Further functionalization of the obtained compounds was carried out.Experimental part. Thiocarbonyl ylide was obtained by fluoride ion-promoted 1,3-desilylation of the known chloromethyl trimethylsilylmethyl sulfide. The synthesis of the target compounds involved the [3+2] cycloaddition of such an ylide to a series of compounds with an activated multiple bond. The stereochemistry of the target compounds was determined by 1H NOESY experiments. Synthetic derivatives of thiolancarboxylic acids, in particular aldehydes, alcohols, amines, amidines, were obtained by functionalization of the [3+2] adducts.Conclusions. The synthetic approach to functionalized tetrahydrothiophenes by the [3+2] cycloaddition reaction of thiocarbonyl ylide with a number of compounds containing an activated multiple bond has expanded the limits of application of this reaction and allows obtaining the target compounds in multigram quantities. A high stereoselectivity of this reaction was observed. The reaction products are convenient synthetic precursors to the various classes of organic compounds.","PeriodicalId":16676,"journal":{"name":"Journal of Organic and Pharmaceutical Chemistry","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87568685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0