Tick-borne encephalitis virus (TBEV) belonging to Flavivirus genus causes severe infection in humans. The search for therapeutically relevant compounds targeting TBEV requires the exploration of novel chemotypes. A versatile synthesis of previously unknown 4-aminopyrimidines and 4-aminopyrimidine N-oxides based on a fluorosubstituted heterocyclic core is described. A representative series of 4-aminotetrahydroquinazoline derivatives, containing aliphatic and aromatic substituents as well as the adamantane framework, was obtained and their activity against tick-borne encephalitis virus reproduction was studied. Nine compounds were found to inhibit TBEV entry into the host cells. A bulky hydrophobic adamantyl group was identified to be important for the antiviral activity. The developed synthetic route allowed an easy access to a consistent compound library for further structure-activity relationship studies.
Palladium-catalyzed arylation of various adamantanecontaining amines with 2-bromopyridine has been studied, and the influence of the phosphane ligand, concentration, and molar ratio of the reagents on the composition of the reaction mixture and on the yield of the target adamantylpyridin-2-amines has been analyzed. The dependence of the formation of N,N-diarylated products on the nature of the starting adamantylamines is shown.
N,N'-bis(bromobenzyl) substituted diazacrown ethers were obtained in the reactions of corresponding free diazacrowns with two equivalents of bromobenzyl bromides in high yields. These compounds were introduced in the Pdcatalyzed amination reaction with 1,3-bis(aminomethyl) and 1,3-bis(2-aminoethyl)adamantanes to give macrobicyclic products. The yields were shown to be dependent on the nature of starting diazacrown derivatives and diamines. N,N'-bis(3-bromobenzyl)
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