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Information × Registration Number 0225U002719, (0123U102102) , R & D reports Title Expanding the synthetically accessible chemical space of organic compounds for the purpose of the new drugs creation. popup.stage_title Структурна ідентифікація «білих плям» в сучасному хімічному просторі. Валідація нових процедур для паралельного синтезу. Визначення будівельних блоків, що потрібні для використання у загальновідомих процедурах, та розробка ефективних методів синтезу останніх. Head Riabukhin Serhii V., Доктор хімічних наук Registration Date 01-04-2025 Organization Taras Shevchenko National University of Kyiv popup.description1 The aim of the project is to expand the synthetically accessible chemical space of organic compounds for the needs of high-throughput screening at the early stages of the new drugs development. The expansion is carried out by filling the so-called "white spots" appearing in the process of analysis with the help of chemoinformatic tools. This will enable us to select an "ideal" million compounds from the existing chemical space, which is a crucial factor for conducting high-quality high-throughput screening, as well as significantly increase the search efficiency for new pharmaceutical substances. popup.description2  In the second stage of the project, our main goal was to develop new preparative methodologies for synthesizing key compounds (building blocks) that fill the "white spaces" in chemical space, as well as methodologies for parallel synthesis, particularly for multi-component reactions where the strategy of creating diversity through new building blocks is ineffective. Specifically, synthetic chemistry based on the stelane (biscnoradamantane) scaffold was deepened and improved, with studies on its stability, storage conditions, tolerance to various chemical transformation conditions, and potential for further functionalization. In addition, an innovative methodology for introducing primary and secondary alkyl substituents at the α-position of the carbonyl group was developed, which effectively expands the chemical space of the corresponding ketone derivatives and significantly increases the diversity of final derivatives in drug screening campaigns. A new method for synthesizing isatins with donor substituents, such as methoxy, hydroxy, mono- and dialkylamino, was developed to diversify the isatin subspace. A key and labor-intensive aspect was the optimization of conditions for synthesizing conformationally constrained spiropyrrolidines. By varying the conditions, it became possible to introduce two substituents or a spirocycle into all positions of proline, which significantly expanded the chemical space of prolines, increased its diversity, and allowed the production of prolines with controlled conformation, which is crucial in medicinal chemistry. Furthermore, a new synthetic process for 3-functionalized 2-pyrrolidones was optimized, involving 3-5 stages, easily scalable to hundreds of grams, and not requiring expensive starting materials. Product Description popup.authors Volochniuk Dmytro M. Hranat Dmytro S. Makhankova Valeriia H. Mytiuk Andrii P. Nosyk Pavlo S. Ostapchuk Yevhen M. Pashchenko Oleksandr Ye. popup.nrat_date 2025-04-01 Close