The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents

Anxiety disorders represent one of the most prevalent categories of psychiatric illnesses, affecting individuals regardless of gender, age, or social standing. They result in substantial personal and societal costs. The pursuit of novel pharmacological approaches for treating these disorders is driven by the increasing medical necessity to enhance the effectiveness and safety profiles of anxiolytic medications. Due to the fact that benzodiazepines and their derivatives have anti-anxiety, hypnotic-sedative, antidepressant, anticonvulsant, and muscle relaxant properties, they occupy a leading place in the treatment of anxiety disorders. An essential aspect of investigating the pharmacological activity of new triazolobenziazepine derivatives is assessing their impact on rodent muscle tone and coordination of movements. The aim of the work is to find out the influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents in the “vertical grid” test and coordination of movements using the rotarod test. Materials and methods. The objects of the study were 5 new derivatives of 1,2,3-triazolo-1,4-benzodiazepines. Before conducting in vivo experiments, these derivatives were mixed with lactose at a ratio of 1:1000. The “vertical grid” test and rotarod test (rotating rod test) were used to reproduce the model of motor behavior of rodents. Results. The presence of a tendency to the manifestation of a myorelaxant effect in the “vertical grid” test was established. The indicator of the total duration of detention at the facilities was similar and did not differ significantly in the control and experimental groups at doses of 0.50 mg/kg and 0.75 mg/kg. Derivatives MA-252, MA-253 and MA-254 at a dose of 1 mg/kg reduced the total duration of retention on the vertical grid, which indicates their mild muscle relaxant effect. In the rotating rod test, MA-253 derivative at a dose of 1 mg/kg increased the retention time on the rotarod, which demonstrates greater physical endurance of the animals of these experimental groups. Conclusions. The study’s findings indicated that the 1,2,3-triazolo-1,4-benzodiazepine derivatives did not exhibit an adverse impact on movement coordination. Some of these derivatives demonstrated a mild muscle relaxant effect. These results support the need for further research into their influence on spontaneous motor activity. Additionally, there’s a necessity to determine the dosage regimen, establish an effective dose, and adapt it for human use

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

Substituted 1H-pyrazolo[3,4-b]pyridine-4- and 1H-pyrazolo[3,4-b]pyridine-6-carboxamides have been synthetized through a Doebner–Ugi multicomponent reaction sequence in a convergent and versatile manner using diversity generation strategies: combination of two multicomponent reactions and conditions-based divergence strategy. The target products contain as pharmacophores pyrazolopyridine and peptidomimetic moieties with four points of diversity introduced from readily available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

The comprehensive review contains the analysis of literature data concerning reactions of heterocyclization of aminoazoles and demonstrates the application of these types of transformations in diversity-oriented synthesis. The review is oriented to wide range of chemists working in the field of organic synthesis and both experimental and theoretical studies of nitrogen-containing heterocycles

Технологія зведення силосів із ЛМК

Metal silos are a modern and popular way of storing grain; Despite the apparent simplicity; they are complex engineering structures that require accurate calculation taking into account all the features of design and construction; operation and location of their location. The choice of silo type is both a problem and a problem: Structurally; modern silos are executed in several variants; depending on the way of storage of products and their removal. The assembly of silos from prefabricated galvanized structures by lifting and raising tiers allows you to perform basic work directly at the level of the construction site.Металеві силоси є сучасним і популярним способом зберігання зерна, Незважаючи на уявну простоту, вони  є складними інженерними спорудами, які вимагають точного розрахунку з урахуванням всіх особливостей проектування та зведення, експлуатації та місця їх розташування. Вибір типу силосу є одночасно і завданням і проблемою: Конструктивно сучасні силоси виконуються в декількох варіантах, в залежності від способу зберігання продукції та її видалення. Зведення силосів із збірних оцинкованих конструкцій методом підйому та підрощування  ярусів  дозволяє виконувати основні роботи безпосередньо на рівні будівельного майданчику

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkyne

Endoscopy and minimally invasive surgery in the diagnosis and treatment of precancerous diseases and cancer of the stomach in the early stages

One of the most urgent problems of modern oncology is cancer of the stomach, which takes one of the leading places in the structure of cancer incidence. Given the high prevalence of gastric cancer and aggressive course of the disease it is extremely necessary to solve the problem of early diagnosis based on evidence-based medicine and meticulously comply with this disease screening protocols. The review highlights the main precancerous processes and conditions prior to the appearance of tumor, especially degeneration of precancerous lesions to cancer. In particular, to precancerous conditions include chronic atrophic gastritis, pernicious anemia, intestinal metaplasia of the gastric epithelium, the appearance of polyps, endured surgery on the stomach, Menetries disease. These diseases with different frequencies give rise to different degrees of severity of dysplasia, and metaplasia of the stomach epithelium, and ultimately cancer. Understanding precancerous states helps to shape risk and carefully carry out the selection of patients for screening activities to develop the tactics of treatment of precancer and early gastric cancer. The standard diagnosis is endoscopy, which allows to perform a biopsy of the alleged pathological focus for subsequent histological examination is necessary for morphological verification of diagnosis and patient management. To improve the method used technique of chromoesdoscopic examination. Thanks to the introduction of new technologies into clinical practice, such as particular zoom magnification endoscopy, endoscopic examination in a narrow spectral range, endoscopic ultrasound, has become possible to more accurately determine the boundaries of the tumor, depth of invasion into the stomach wall and correctly assess the state of the regional lymph nodes. Diagnosis of early forms of gastric cancer has opened opportunities for sparing endoscopic interventions, namely endoscopic mucosal resection of the stomach, endoscopic submucosal dissection by layer, photodynamic therapy and laser destruction. All these techniques can improve patient survival and quality of life by improving the methods for early diagnosis of the disease and organ sparing surgery