PreprintArticleVersion 1This version is not peer-reviewed
Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2, 4]triazino[2,3-C]quinazolines
Version 1
: Received: 7 October 2024 / Approved: 7 October 2024 / Online: 8 October 2024 (11:14:15 CEST)
How to cite:
Grytsak, O.; Schabelnyk, K.; Severina, H. I.; Ryzhenko, V.; Voskoboynik, O.; Belenichev, I.; Kovalenko, S.; Oksenych, V.; Kamyshnyi, O. Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2, 4]triazino[2,3-C]quinazolines. Preprints2024, 2024100540. https://doi.org/10.20944/preprints202410.0540.v1
Grytsak, O.; Schabelnyk, K.; Severina, H. I.; Ryzhenko, V.; Voskoboynik, O.; Belenichev, I.; Kovalenko, S.; Oksenych, V.; Kamyshnyi, O. Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2, 4]triazino[2,3-C]quinazolines. Preprints 2024, 2024100540. https://doi.org/10.20944/preprints202410.0540.v1
Grytsak, O.; Schabelnyk, K.; Severina, H. I.; Ryzhenko, V.; Voskoboynik, O.; Belenichev, I.; Kovalenko, S.; Oksenych, V.; Kamyshnyi, O. Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2, 4]triazino[2,3-C]quinazolines. Preprints2024, 2024100540. https://doi.org/10.20944/preprints202410.0540.v1
APA Style
Grytsak, O., Schabelnyk, K., Severina, H. I., Ryzhenko, V., Voskoboynik, O., Belenichev, I., Kovalenko, S., Oksenych, V., & Kamyshnyi, O. (2024). Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2, 4]triazino[2,3-C]quinazolines. Preprints. https://doi.org/10.20944/preprints202410.0540.v1
Chicago/Turabian Style
Grytsak, O., Valentyn Oksenych and Oleksandr Kamyshnyi. 2024 "Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2, 4]triazino[2,3-C]quinazolines" Preprints. https://doi.org/10.20944/preprints202410.0540.v1
Abstract
Designing novel biologically active compounds with anti-inflammatory properties based on condensed quinazolines is a significant area of interest in modern medicinal chemistry. In the present study, we describe the development of promising new bioactive molecules through the bioisosteric replacement of a carbon atom with a sulfur atom in anti-inflammatory agents, specifically 3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)butanoate. Design and synthetic studies have led to the series of previously unknown substituted 2-[((3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)methyl)thio]carboxylic acids and their esters. These compounds were synthesized by reacting 6-chloroalkyl-3-R-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones with mercaptoalkyl carboxylic acids and their functional derivatives. The purity and structure of the obtained compounds were confirmed using a set of physicochemical methods, including elemental analysis, HPLC-MS, and 1H NMR spectroscopy. Molecular modeling, predicted toxicity, drug-likeness and pharmacokinetics data were used to select compounds for evaluation of their effects on acute aseptic inflammation (carrageenan-induced paw edema test) and on markers of the inflammatory process. The compound 2-((1-(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)ethyl)thio)acetic acid (compound 2.5) was identified as the most active anti-inflammatory agent, demonstrating significant inhibition of both paw edema development and the generation of pro-inflammatory cytokines and mediators. Results from docking studies and analysis of "structure-affinity" correlations revealed that these compounds are promising candidates for further modification and detailed investigation of their anti-inflammatory activity
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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