Synthesis of novel potential HDAC inhibitors based on multicomponent reactions

Multicomponent reactions (MCRs) provide valuable opportunities for the synthesis of a wide range of heterocyclic compounds, many of which exhibit significant biological activity and unique physical properties. Compared with traditional step-by-step synthetic methods, MCRs represent a powerful tool for constructing diverse organic frameworks. These reactions enable the preparation of valuable organic compounds in a relatively simple, one-step process that often affords high yields and eliminates the need for intermediate purification. This efficiency not only saves time but also makes the synthesis of target molecules faster and more cost-effective. Numerous derivatives obtained through multicomponent reactions possess pharmacologically important properties. Among them are nitrogen-containing compounds such as triazole-, pyrrole- , indole derivatives, etc. Several of these derivatives have been developed into clinically approved drugs used as antibacterial (Essarmycin), antipsychotic (Molindone), anticancer (Pemetrexed), and antiviral (Toyocamycin) agents, as well as treatments for Hepatitis C (Telaprevir®, Victrelis®) and beta blockers (Pindolol). However, many potential derivatives remain unexplored, emphasizing the importance of continued research into new heterocyclic frameworks. The first part of this thesis reviews both the earliest and recent literature on the synthesis and modification of triazolo[1,5-a]pyrimidine, 4,5,6,7-tetrahydroindole, and pyrrolo[2,3-d]pyrimidine scaffolds, as well as the properties and applications of their derivatives. The second part presents our approaches to the synthesis of these compounds via multicomponent one-pot reactions, along with the modification of triazolo[1,5-a]pyrimidine and 4,5,6,7-tetrahydroindole derivatives. Molecular docking studies were performed for selected triazole-containing compounds, and the results are discussed in the experimental section. Additionally, their predicted Sirtuin-2 inhibitory activity was evaluated experimentally. Finally, the synthetic procedure for pyrrolo[2,3-d]pyrimidine derivatives was optimized, leading to the preparation of several new compounds within this series.