Phase transfer catalysis (PTC) is an excellent possibility in the synthesis of organic compounds as it allows the reactions to be carried out under the conditions of green chemistry, while maintaining high yields and selectivity. The great advantage of these reactions is also the possibility of carrying out the reactions not only under conventional conditions, but also mechanochemically in solvent-free processes. Bearing this in mind, we decided to develop a new method for the synthesis of known biologically active compounds from the group of long-chain arylpiperazines (LCAPs). The first mortar trials were very promising and prompted us to carry out a series of ball mill reactions. One of the technological problems that we encountered while conducting reactions in the ball mill was the difficulty in extracting the post-reaction mixture. We tested the effects of additives improving the insulation of the product, such as, e.g., starch, zeolites, and silica. Research has proven that with appropriate process conditions using TBAB as a catalyst and in the presence of potassium carbonate and a small amount of Zeolite ZSM5 or silica, aripiprazole can be obtained with a yield of 90% in just five minutes. The obtained results are very promising and it is worth considering them as an alternative to the synthesis of other compounds from the LCAPS group.

1,3,5-triazine derivatives are useful compounds with potential applications in various branches of chemical industry, including pharmaceutical chemistry, cosmetic chemistry, photochemistry, and organic chemistry. Due to the growing environmental requirements on conducting efficient, economical, and safe syntheses, development of new methods for synthesizing organic compounds is highly desirable. In this publication, we present a protocol for the synthesis of 1,3,5-triazine derivatives using a sonochemical approach. In as little as 5 min, it is possible to obtain most of the investigated compounds with a yield of over 75%. An undeniable advantage of this method, besides its short time, is the use of water as the solvent. Furthermore, we provide examples that the sonochemical method may be more versatile than the competing microwave method. Analysis conducted using the DOZN^TM 2.0 tool revealed that in terms of the 12 principles of green chemistry, the developed sonochemical method is 13 times "greener" than the classical one. Additionally, it has been demonstrated that the investigated molecules are attractive for their application as drug-like compounds.

Considering the key functions of the 5-HT₇ receptor, especially in psychiatry, and the fact that effective and selective 5-HT₇ receptor ligands are yet to be available, in this work, we designed and synthesized novel 1,3,5-triazine derivatives particularly based on the evaluation of the effect of substituents at aromatic rings on biological activity. The tested compounds showed high affinity to the 5-HT₇ receptor, particularly ligands N²-(2-(5-fluoro-1H-indol-3-yl)ethyl)-N⁴-phenethyl-1,3,5-triazine-2,4,6-triamine 2 (K_i = 8 nM) and N²-(2-(1H-indol-3-yl)ethyl)-N⁴-(2-((4-fluorophenyl)amino)ethyl)-1,3,5-triazine-2,4,6-triamine 12 (K_i = 18 nM) which showed moderate metabolic stability, and affinity to the CYP3A4 isoenzyme. As for the hepatotoxicity evaluation, the tested compounds showed moderate cytotoxicity only at concentrations above 50 µM. Compound 12 exhibited less cardiotoxic effect than 2 on Danio rerio in vivo model.

Alzheimer's disease is a neurodegenerative condition with no effective cure, and current therapies, like donepezil, only alleviate symptoms. Research has explored cholinesterase inhibitors and strategies targeting tau protein, often combining inhibitors with 5-HT receptor antagonists, particularly 5-HT₆. However, dual-action BuChE inhibitors and 5-HT₇ antagonists have not been studied until now. This study evaluated such compounds in an animal model, focusing on two candidates: compound 18 (BuChE IC₅₀ = 4.75 μM; 5-HT₇K_i = 7 nM) and compound 50 (BuChE IC₅₀ = 2.53 μM; 5-HT₇K_i = 1 nM). Compound 50 showed robust cognitive improvements, enhancing memory consolidation and acquisition, particularly in reversing scopolamine-induced deficits. In contrast, compound 18 exhibited limited or dose-dependent efficacy, potentially limiting its applicability. These findings highlight the strong potential of compound 50 for cognitive enhancement therapies and suggest it warrants further investigation.

Colorectal cancer (CRC) remains a major global health challenge, necessitating the development of more effective and environmentally sustainable treatments. This study presents a novel green synthetic protocol for 1,3,5-triazine derivatives with anticancer potential, employing both microwave-assisted and ultrasound-assisted methods. The synthesis was optimized using 4-chloro-N-(2-chlorophenyl)-6-(morpholin-4-yl)-1,3,5-triazin-2-amine as the key intermediate, with sodium carbonate, TBAB, and DMF providing optimal yields under microwave conditions. To enhance sustainability, a modified sonochemical method was also developed, enabling efficient synthesis in aqueous media with a minimal use of organic solvents. A series of nine morpholine-functionalized derivatives were synthesized and evaluated for cytotoxic activity against SW480 and SW620 colorectal cancer cell lines. Compound 11 demonstrated superior antiproliferative activity (IC₅₀ = 5.85 µM) compared to the reference drug 5-fluorouracil, while compound 5 showed promising dual-line activity. In silico ADME analysis supported the drug likeness of the synthesized compounds, and biomimetic chromatography analysis confirmed favorable physicochemical properties, including lipophilicity and membrane affinity. These results underscore the potential of the developed protocol to produce bioactive triazine derivatives through an efficient, scalable, and environmentally friendly process, offering a valuable strategy for future anticancer drug development.