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Information × Registration Number 0225U000279, (0124U003760) , R & D reports Title Atypical framework compounds as a new advanced platform for drug discovery popup.stage_title Розробка методологій синтезу ключових каркасних сполук та їх функціональних похідних Head Riabukhin Serhii V., Доктор хімічних наук Registration Date 08-01-2025 Organization Taras Shevchenko National University of Kyiv popup.description1 Proving the hypothesis of bioisosterism of derivatives of polycyclic framework compounds in relation to benzene and adamantane when they are used in medicinal products, as well as creating a complex toolkit for evaluating any polycyclic frameworks for suitability to the needs of the modern search for new drugs, which can be solved by developing scalable methods of synthesis of the latter and establishing the dependence of ADME-tox parameters on structural factors popup.description2 The project is aimed at developing modern, scalable and efficient approaches to the synthesis of little-studied three-dimensional polycyclic skeleton compounds, structurally close to adamantane, cubane, as well as their heteroatom-containing analogues. These compounds are promising bioisosteres of benzene and adamantane nuclei, which have the potential to improve the pharmacokinetic profile and metabolic stability of potential drugs obtained as a result of the corresponding bioisosteric substitutions. It is planned to obtain a number of such compounds in multigram quantities. Their physicochemical properties and ADME-tox characteristics will be studied by experimental methods suitable for determining key pharmacokinetic parameters such as measuring metabolic stability in microsomes, stability in plasma, permeability through model barriers (PAMPA, Caco-2), etc. Structural features will be investigated using X-ray structural analysis. In addition, computational chemistry methods (DFT and ab initio) will be used for modeling and predicting properties. Based on the obtained framework amines and carboxylic acids, mini-libraries of potentially biologically active derivatives will be created, the comprehensive study of which will allow choosing optimal synthetic and computational approaches for predicting the properties of new analogues in the future. The final result will be the creation of scalable synthetic protocols for obtaining little-studied (atypical) framework compounds and their derivatives; the formation of clear criteria and practical tools for the introduction of atypical framework nuclei into pharmaceutical developments; acceleration of the search for new bioactive compounds and improvement of their efficiency.  Product Description popup.authors Burianov Volodymyr V. Haidai Oleksandr V. Hryhoriev Nazar Е. Liapunov Оleksadr Yu. Pashchenko Oleksandr Ye. Popov Ioann O. Smyrnov Oleh K. Frolov Andrii I. popup.nrat_date 2025-01-08 Close