Oleksandr Grygorenko, Dr. Sci., Ph. D., Assoc. Prof.
This research area emerged from the study of unnatural (mostly bicyclic) amino acids back in late 2000s. Currently, we mainly focus on design and synthesis of chemical building blocks (i.e., functionalized derivatives used to introduce a required structural fragment into the target compound) for early drug discovery. Other areas of interest include ultra-large chemically accessible compound libraries and cheminformatics tools to assess the compound’s lead-likeness.
Our design of building blocks is based on a combination of design concept that appeared at the edge organic and medicinal chemistry recently: target-oriented synthesis, diversity-oriented synthesis, and lead-oriented synthesis. Most significant to us, lead-oriented synthesis, focuses on the compound’s physicochemical and structural properties at the earliest steps of the study. That is why we aim at low-molecular-weight hydrophilic sp3-enriched carbo- and heterocyclic or heteroaromatic derivatives with one or two functional groups useful for parallel synthesis. As mentioned above, we started research in this area with design and synthesis of bicyclic saturated amino acids and their analogs. To date, the range of chemotypes we are interested in is very large; some recent examples include:
fluorinated sp3-enriched compounds;
sp3-enriched boronic derivatives;
saturated organosulfur building blocks;
novel mono- and spirocyclic derivatives of small rings;
motifs previously underrated in medicinal chemistry, e.g. phosphine oxides, sulfoximines, etc.
We aim at extending the scope of chemical building blocks for early drug discovery by developing new chemotypes that follow (or possibly even create) the newest trends in medicinal chemistry, as well as by filling the "gaps" in the existing chemical space. Also, we want to understand the effect of the developed building blocks or their major structural elements on the relevant physico-chemical properties (such as pKa and LogP), as well as chemical reactivity in further parallel synthesis. We already started doing that for the fluorinated sp3-enriched derivatives. In the field of chemically tractable ultra-large compound libraries, we are interested in applications of machine learning methods to the chemical space created (in collaboration with specialists in the respective areas).
We have strong collaborations with Enamine Ltd., Chemspace, as well as Institute of Organic Chemistry and V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, all based in Kyiv (Ukraine). In addition to that, we are expanding international collaboration geography, that currently include Spain: University of Zaragoza (Prof. Carlos Cativiela), Basque center for materials, applications & nanostructures (Dr. Stefan Wuttke); Germany: Leibniz Institute of Molecular Pharmacology (Prof. Margitta Dathe), Max Planck Institute for Coal Research (Prof. Benjamin List, Nobel Laureate), University of Munster (Prof. Gunter Haufe), Max Planck Institute of Molecular Physiology (Prof. Herbert Waldmann); USA: University of Iowa (Prof. M. Ashley Spies), Harvard Medical School (Dr. Christoph Gorgulla), Carnegie Mellon University (Dr. Oleksandr Isayev), Stony Brook University (Prof. Dmytro Kozakov), University of Chicago (Prof Mark Levin); Canada: University Laval (Prof. Thierry Ollevier).
