bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study acute toxicity of 4-(R-amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol in vivo
Authors: Safonov A. A. 
Published: March 2019

Typically, the system is already known are used as the core for a new substance, which have already proved themselves as potential drugs. So one of these is 1,2,4-triazole ring.
The purpose was to study acute toxicity of 4-((R-iden)amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiols and identify possible patterns acute toxicity of the chemical structure of indicators derivatives. In the study of acute contact toxicity was used spreadsheet rapid method for Prozorovsky V. B.
Analysis of the results of studies acute toxicity of 1,2,4-triazole derivatives showed that all substances are relate to the 4th class of toxicity according to K. K. Sidorov. Their toxicity is in the range 357 ± 28–1 250 ± 220 mg/kg.
Introduction in a molecule 4-amino-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thiol nitrobenzylidene, dimethylaminobenzylidene, 2-chloro-6-fluorobenzylidene substituent leads to a reduction of acute toxicity to the 566–576 mg/kg. Replacement of 2-chloro-6-fluorobenzylidene radical in a molecule 4-((2-chloro-6-fluorobenzylidene)amino)-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thiol at 4-fluorobenzylidene, 3,4-difluorobenzylidene, 4-methoxybenzylidene, 3,5-dimethoxybenzylidene leads to further reduce toxicity.
Introduction methyl radical in a molecule 4-(benzylidene)amino)-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thiol and 4-((4-fluorobenzylidene)amino)-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thiol resulting to increased toxicity.
It was established that the most toxic substance among the test compounds is 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol. Its LD50 is 357 ± 28 mg/kg and the least toxic compound 4-((3,4-difluorbenzylidene)amino)-5-(thiophen-2-ilmethyl)-4H-1,2,4-triazole-3-thiol, LD50 1 250 ± 220 mg/kg.
Development of recommendations on creating local formulary drug list for children affected with gastritis and duodenitis
Authors: Trokhymchuk V. V. , Vyshnytska I. V. 
Published: March 2019

An urgent task is to carry out regular quality control and rational prescribing of drugs, changes to the drug formulary lists for the purpose of positive influence on the processes of pharmaceutical provision, especially children affected with gastritis and duodenitis.
The aim of the work was to create a list of the recommended groups of drugs for further development of the local insurance and formulary drug lists used for treatment of children with gastritis and duodenitis using modern information technologies. Methods of peer reviews, questionnaires, direct observation, modeling, and information analysis were used in the process. The objects of study were regulatory and legislative documents, medication treatments sheets, price lists of wholesale pharmaceutical companies, forms of expert assessments.
Science-based guidelines for the assessment of the economic costs for the inclusion of medicines in local formulary drug lists of health care institutions to help children with gastritis and duodenitis in the acute stage, in specialized hospitals, taking into account peculiarities of the disease under study at the regional level were formed.
According to the results of a comprehensive study of pharmaceutical provision for treatment of children with gastritis and duodenitis, in addition to an expert evaluation of medicines, recommendations for the creation of a local formulary drug list were made and recommended list of drug groups was determined by 15 INN drugs to be used in the development of a local drug formulary list for pharmacotherapy of the pathology under study.
Synthesis and biological properties of 7-(2-hydroxy-3-m-ethylphenoxypropyl-1-)theophilline derivatives
Authors: Ivanchenko D. G. 
Published: March 2019

Various origin antibiotics and many other chemotherapeutic agents, which are based on the heterocyclic compound, found wide application in the treatment of infectious diseases. Purine derivatives have long been used in medical practice as antiviral agents (acyclovir, gancyclovir, etc.), and further research to find new antimicrobial and antiviral agents in the row of purine derivatives are justified and perspective.
The aim of this paper is to elaborate simple laboratory methods of 7,8-disubstituted theophylline synthesis, unspecified in scientific papers earlier, and to study their physical and chemical properties.
The melting point has been determined by open capillary method on the device PTP (M). Elemental analysis has been performed on the device Elementar Vario L cube. NMR spectra have been taken using spectrometer Bruker SF-400.
For the initial screening study of the newly-synthesized substances benchmark testing-cultures of both gram-positive and gram-negative bacteria have been used, which belong to clinically significant groups of infections agents which are differing by their morpho-physiological properties.
Heating of 8-bromotheophilline with m-ethylphenoxymethyloxyrane in propanol-1 environment results in formation of 8-bromo-7-(2-hydroxy-3-m-ethylphenoxypropyl-1-)theophylline. Its reactions with primary and secondary amines proceed at boiling in aqueous dioxane environment to form the corresponding 8-aminoderivatives. The heating of initial syntone with 2-ethylpiperidine leads to the formation of oxazoline xanthine.
By applying such computer programs as ALOGPS, DRAGON, GUSAR and ACD/Percepta Platform was established viability of further biological and toxicological in vitro and in vivo research.
Simple laboratory method has been elaborated to synthesize 8-bromo-7-(2-hydroxy-3-m-ethylphenoxypropyl-1-)theophylline, which is initial compound for further synthesis of various theophylline N-, O-, S-substituted.
Reactions of 8-bromo-7-(2-hydroxy-3-m-ethylphenoxypropyl-1-)theophylline with primary and secondary amines have been investigated. As a result 8-aminosubstituted of 7-(2-hydroxy-3-m-ethylphenoxypropyl-1-)theophylline and 6,8-dimethyl-2-m-ethylphenoxymethyl-2,3-dihydro-1,3-oxazolo[2,3-f]theophylline have been synthesized. NMR-spectral characteristics of new synthesized compounds have been studied.
Molecular and pharmacological descriptors (LogP, TPSA, A) to forecast properties of the obtained substances have been calculated, in addition to acute toxicity index. The perspective of the obtained substances using as antistaphylococcal and antifungal agents has been shown.
Development of emulgel technology with saw palmetto extracts and of japanese sophora tincture for androgenetic alopecia treatment
Authors: Yarema I. O. , Feodorovska M. I. , Polovkо N. P. 
Published: March 2019

Androgenic alopecia is a hair disease caused by an excessive influence of androgens on hair follicles, whose treatment requires long-term use of systemic and / or local action drugs. In Ukrainian pharmaceutical market for the androgenic alopecia treatment synthetic drug minoxidil is presented, which in the local long-term application causes many side effects. Therefore, the drugs development of plant origin is important.
Taking into account of the androgenic alopecia pathogenesis, it was developed the emulgel composition and technology, which has Saw Palmetto extract and Sophora Japonica tincture as active ingredients. Their main biological active substances applying topically provide anti-androgenic, venotonic and follicles protective action.
The qualities of dermatological remedies in large measure are influenced by their technological process. Therefore, the purpose of this investigation was the development of a rational emulgel technology with Saw Palmetto extract and Sophora Japonica tincture for the androgenic alopecia prevention and treatment.
Samples of emulgel were manufactured with applying of different technological methods, namely: the method of emulsification, temperature, rate and duration of stirring. Prepared samples were controlled by uniformity, dispersion degree (with microscope Delta Optical Genetic Pro, Poland), pH (with pH-meter 150 MI, Russia) and structure viscosity (with rotational viscometer Brookfield VR-3000, Myr VISKOTECH, Spain).
The optimal temperature for the emulgel preparation is 60 °C, since the melting temperature of cetyl alcohol (the most refractory component of the formulation) is 52 °C. When choosing the emulsifying method it was found that sequential addition of hydrophilic and oil phases to emulgators provided the highest dispersion and optimally rheological properties of the emulgel.
The best homogenization speed, providing a high degree of dispersion and structural viscosity in the range 3 200–3 400 mPas, is 2 000 rev/min. The intensive size reduction of the dispersed phase was observed for 30 min stirring.
As a result of investigation, it was established that the best method of emulsification was the sequential adding of oil and aqueous phase to the mixture of emulsifiers at the temperature – 60 °C, the speed – 2 000 rev/min for 30 min.
Synthesis and physicochemical research of some 2-((5-((theophylline-7'-yl)methyl)-4-R-4H-1,2,4-triazole-3-yl)thio)acetohydrazide ylidenderivatives
Authors: Gotsulya A. S. , Knyazevich P. S. , Panasenko O. I. , Knysh Е. G. 
Published: March 2019

The rapid development pace of the pharmaceutical science constantly increases the demand for new kind of medicine featured with high biological activity and non-toxicity at the same time. Setting the aim to enlarge the amount of scientific findings in the domain of biologically active substances, 1,2,4-triazole and theophylline were used as the starting material. These compounds form the basis for the majority of drugs, such as diuretics, antifungal and antibacterial medicaments. The combination of heterocycles put under research demonstrate a repeated probability increase in the variety of activities. Therefore, the relevance of the following study is determined by valuable properties of these substances. Besides that, the presence of a hydrazide element accounts for a high probability level of antimicrobial, particularly anti-tuberculosis activity.
In order to identify optimal conditions for the synthesis and physicochemical property research, 2-((5-((theophylline-7'-yl)methyl)-4-R-4H-1,2,4-triazole-3-yl)thio) acetohydrazide ylidenderivatives were obtained.
The process of production was carried out through long chain reactions, using the sodium salt of theophylline as a substrate. The conversion is well known being described in many papers. Hydrazide was taken as the starting compound. It was dissolved in water-alcoholic medium while separately, aldehyde was dissolved or mixed in ethyl alcohol as well. The resulting solutions were decanted. The precipitate formed immediately or after a certain period of time, which is likely due to the state of matter of the starting aldehyde.
10 compounds (light-yellow crystalline materials with sharp melting point) were synthesized after that. Their structures and physicochemical properties were confirmed with modern methods of analysis. It is established that the reaction proceeds rapidly with a yield of 77‒95% in water-alcoholic medium at a temperature of about 80 °C.
Synthesis and structural features of 5-(4-(tert-butyl) phenyl)-4-((R)amino)-4H-1,2,4-triazole-3-thiols
Authors: Aksyonova-Seliuk I. I. , Panasenko O. I. , Knysh E. G. 
Published: March 2019

Chemistry of heterocyclic compounds is one of the most popular sector in organic chemistry. Scientists allocate among them a class of derivatives of 1,2,4-triazole. This class of compounds attracts attention his broad spectrum of biological activity. There are antiviral, anti-inflammatory, anti-tubercular, antimicrobial, antioxidant, actoprotective, anti-cancer and other activities. The derivatives of 1,2,4-triazole have one more important advantage. It is low toxicity. This properties do this class of derivatives promising for researches their chemical structure and biological activity and purposeful search of biologically active substances.
The purpose of the work is synthesis of 5-(4-(tert-butyl)phenyl)-4-((R)amino)-4H-1,2,4-triazoles-3-thiols from appropriate ylidene derivatives of 4-amino-5-(4 (tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol and research of their physical and chemical properties.
The objects of research were 10 new compounds, derivatives of 4-amino-5-(4-(tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol. These compounds are the crystal substances which are odorless, insoluble in water and soluble in organic solvents. Investigation of the physical and chemical properties of this compounds was carried out according to the methods listed in the State Pharmacopoeia of Ukraine. The melting temperature of synthesized compounds was determined by device OptiMelt Stanford Research Systems MPA100. The structure of the compound was confirmed by 1H-NMR spectroscopy (Mercury 400) and gas chromatography-mass spectrometry (Agilent 1260 Infinity HPLC).
10 new compounds, derivatives of 4-amino-5-(4-(tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol, were synthesized in a study. The chemical structure of the new compounds was confirmed by modern instrumental methods of analysis. Results of the done work can be use in the future search of biologically active substances.
Study of influence of the surface-active substances concentration on releasing of praziquantel from the rectal suppository
Authors: Romanina D. M. , Berdey I. I. , Gladishev V. V. , Lisyanska G. P. 
Published: March 2019

Acne dermatosis (rosacea, perioral dermatitis, seborrheic dermatitis etc.) are one of the most actual problem in dermatology. Praziquantel is an antiparasitic medication effective towards trematodes, cestodes. Investigations developed by domestic scientists revealed antidemodicosis activity of praziquantel. Use of semisolid dosage forms for rectal administration will allow to increase its efficacy and minimize the risks of adverse reactions.
On the department of technology of medications Zaporizhzhia State Medical University research of development of praziquantel rectal dosage form for therapy of acne dermatosis, complicated with demodicosis, and its technology is carried out. As a result of biopharmaceutical investigations it was determined that combination of excipients – the base (confectionary fat 60%, 10% paraffin, 30% cocoa butter) and surfactant (distilled monoglycerides) provides with the optimal praziquantel releasing.
The aim of this work is study of excipient using in manufacturing of suppository (bases and surfactants) influence on the biopharmaceutical characteristics of praziquantel rectal dosage form.
Investigation was carried out by the one-factors dispersive analysis with repeated observations By way of a parameter of optimization praziquantel releasing was chosen as the first step of bioavailability investigation. Praziquantel releasing from suppository was studied by the equilibrium dialysis by Kruvchinsky’s method at temperature 37 ± 0,5 °С through a cellophane semipermeable membrane «Kuprofan» film using Franz diffusion cell apparatus. Ethyl alcohol was chosen as a dialysis medium considering the solubility of praziquantel. Concentration of released praziquantel after 30 minutes of the dialysis was determined by spectrophotometric analysis.
As a result of biopharmaceutical investigation of praziquantel suppositories it was determined that surface-active substances (distilled monoglycerides) concentration has a statistically significant influence on its releasing from rectal dosage form. It was ascertained that 0,5% concentration of distilled monoglycerides provides with the optimal releasing of praziquantel from rectal suppositories.
Synthesis and hypoglycemic activity of 7-n-butyl-3-methyl-8-thioxanthine derivatives
Authors: Romanenko M. I. , Ivanchenko D. G. , Sharapova T. A. , Bilay I. M. , Aleksandrova K. V. 
Published: March 2019

According to the International Diabetes Federation in 2015 were registered 59.8 million patients with diabetes in Europe. Synthetic drugs are widely applied in addition to a variety of insulins to normalize blood glucose level. It should be noted that the oral anti-diabetic drugs are the common therapeutic agents for the treatment of diabetes mellitus type II, and therefore the search for new non-toxic hypoglycemic agents is one of the most urgent problems of modern pharmaceutical science. It is known that 7,8-disubstituted xanthine derivatives exhibit hypoglycemic activity.
The aim of this work lies in developing unique method to synthesize undocumented in other scientific papers 7-n-butyl-3-methyl-8-thioxanthine derivatives and also studying of their hypoglycemic activity.
Acute toxicity of synthesized compounds has been studied with the application of Prozorovsky’s method. The glucose homeostasis characteristic has been performed on carbohydrate tolerance that has been determined by the glucose load test on the control group and on the intact rats.
The reactions of 7-n-butyl-3-methyl-8-thioxanthine with benzylchlorides, bromoketones, esters and an amide of chloroacetic acid have been studied. Reactions of mentioned syntons proceed smoothly in aqueous propanol-2 environment and lead to the formation of the corresponding 8-benzyl-, benzoylmethylthioxanthines and xanthinyl-8-thioacetic acid derivatives.
Accessible laboratory method has been elaborated to synthesize unspecified in scientific papers earlier 8-thiosubstituted 7-n-butyl-3-methylxanthine by reacting 7-n-butyl-3-methyl-8-thioxanthine with benzylchlorides, bromoketones, esters and an amide of chloroacetic acid, their structure having been proved by NMR-spectroscopy data. The acute toxicity of synthesized compounds has been studied. It has been established that LD50 is in the range 820–2477 mg/kg, i. e. obtained substances are low-toxic and practically non-toxic according to Sidorov’s classification. Also the study of hypoglycemic activity of synthesized compounds has been carried out. A significant perspective for further research to find the original antidiabetic agents has been shown by bioassay results. It has been found that 7-n-butyl-3-methylxanthinyl-8-thioacetamide is more active than reference substances.
Keududukan Hukum Para Pihak dalam Sengketa Tanah dan Bangunan Benteng Pendem Ngawi-Ex Knil Belanda
Authors: . Karyoto , . Nurbaedah , . Sholahuddin 
Published: March 2019

Penelitian ini dilatarbelakangi sengketa tanah dan bangunan Benteng Pendem Ngawi di Kabupaten Ngawi yang sekarang menjadi polemik beberapa pihak yang mengklaim lebih layak untuk mengusai tanah tersebut, yaitu TNI AD Kodam V/Brawijaya Cq Batalyon Armed Ngawi, Pemerintah Daerah Kabupaten Ngawi dan Kementerian Hukum dan HAM, Cq Lembaga Pemasyarakatan Kabupaten Ngawi. Rumusan masalah penelitian ini adalah bagaimana keududukan hukum para pihak dalam sengketa tanah dan bangunan Benteng Pendem Ngawi-Ex Knil Belanda di Kabupaten Ngawi. Penelitian ini menggunakan metode legal research (normatif) dengan pendekatan kasus, yang dalam hal ini menjadikan kasus sengketa tanah dan bangunan benteng Pendem Ngawi di Kabupaten Ngawi sebagai objek dasar kajian penelitian. Bahan hukum penelitian ini terdiri dari bahan hukum primer yang dalam hal seperti Peraturan Pemerintah Nomor 24 Tahun 1997 tentang Pendaftaran Tanah, Kitab Undang-Undang Hukum Perdata (KUHPer/BW) serta Peraturan Menteri Agraria/Kepala Badan Pertananahan Nasional Nomor 3 Tahun 1997. Kemudian bahan skunder terdiri dari dokumen-dokumen resmi, meliputi karya tulis, buku-buku teks, jurnal-jurnal hukum dan komentar-komentar atas putusan pengadilan, serta terakhir adalah bahan non-hukum, yaitu bahan yang memberikan penjelasan maupun petunjuk terhadap bahan hukum primer maupun sekunder yang telah ada seperti Kamus Besar Bahasa Indonesia. Hasil penelitian menunjukkan bahwa kedudukan hukum TNI AD KODAM V/Brawijaya Cq Batalyon Armed Ngawi dalam penguasaan tanah dan bangunan banteng adalah sah hal tersebut didasarkan pada hak okupasi tanah dan bangunan Benteng Pendem Ngawi yang diperoleh pada saat Negara dalam Keadaan Darurat Militer. Kemudian untuk kedudukan hukum Pemerintah Daerah Kabupaten Ngawi, secara Administrasi memang tidak memiliki dokumen data tanah dan Bangunan Benteng Pendem Ngawi, namun demikian Pemerintah Daerah Kabupaten Ngawi berwenang untuk melestarikan Peninggalan sejarah Purbakala sebagai Budaya bangsa yang harus diamankan dan dijunjung tinggi. Terkait kedudukan Lembaga Pemasyarakatan Ngawi (LP Ngawi) dalam penguasaan tanah tersebut bahwa menurut catatan yang ada sejak jaman Kolonial Belanda oleh Dep.V.Oerlog telah diserahkan kepada Dep. V. Justitie dan sejak itu telah berpuluh puluh tahun lamanya dikuasai dan diawasi oleh LP. Ngawi dan hal tersebut diperkuat dengan dokumen data tanah dan bangunan Benteng Pendem Ngawi.
ДОСЛІДЖЕННЯ ПРОБЛЕМИ ПРОЕКТУВАННЯ НАД-ЛЕГКИХ ЛІТАКІВ З УРАХУВАННЯМ ВИМОГ СПОЖИ-ВАЧА
Authors: Нечипорук Микола Васильович , Поліщук Олена Олексіївна , Полупан Антон Сергійович 
Published: March 2019

The article deals with the issues of improving the methods of forming accounting for ultralight aircraft. The article provides information on the identification of ultralight aircraft according to the classification of the International Aviation Federation (IAF) and the laws of Ukraine. It is analyzed the market for ultralight aircraft , the main manufacturers of ultralight aircraft in the world are identified. It is identified the main categories of consumers of ultralight aircraft. It is highlighting the perspectives and main problems of the development of ultralight aviation in Ukraine and the world and stages of the design of ultralight aircraft. Attention is focused on the practice of global aviation industry, which suggests that gaining new positions and supporting competitiveness of production in the market requires continuous improvement of aircraft quality and the creation of innovative technologies in the face of stringent requirements for scientific, technical, technological, organizational, economic, personnel and investment support for design and aircraft manufacturing. The solution to this problem is primarily related to the effectiveness of the steps taken by the designer, the improvement of production processes and manufacturing technology. Determined by the most promising solution to reduce economic risks and control the level of demand is to attract the customer (consumer) in the process of designing aircraft products. The research objectives are defined and solutions are proposed for improving the design quality of ultralight airplanes by introducing consumer criteria into the design process of ultralight airplanes to meet a wide range of applications. The use of the obtained solutions will allow the manufacturer to make more effective design decisions on the design of ultralight aircraft. Research will further improve the methods of forming ultra-light aircraft in the early design stages
Prototype of Strategic Information System Used for Marketing Funnel: Study Case at Fusion Payments – a Fin Tech Startup
Authors: Syafa`.at Agus 
Published: March 2019

Nowadays E-Commerce business is appealing for majority investor. Almost every month, we hear new startup iscreating a new innovative product ready to be released into the market. There are many types of of startup with vary types of business, such as marketplace, ecommerce, etc. With limited resources and budget, it is very essential for a startup to begin the journey with the the right information and IT Strategic Planning. The aim is to have clear goals and framework before developing the business into real product.