Novel Benzylic Substituted Imidazolinium, Tetrahydropyrimidinium and Tetrahydrodiazepinium Salts: Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors

The new imidazolinium, tetrahydropyrimidinium and tetrahydrodiazepinium salts were synthesized in good yield by the reaction of the corresponding N,N’‐dialkylalkanediamine with triethyl orthoformate in the presence of ammonium chloride. All of the compounds were obtained, and spectroscopically characterized. The crystal structure for the 1,3‐bis(4‐benzyloxy‐3‐methoxybenzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride (5 g) was determined by single‐crystal X‐ray diffraction. The biological properties of all novel compounds were tested and the influence of ring size and benzylic N‐substituents on the biological activities were examined. Also, they were found as effective inhibitors against cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzyme. Among these compounds, 1,3‐bis(4‐(1‐piperidinyl)benzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride (5 f) demonstrated the the best inhibition effects against hCA I, 1,3‐bis(4‐benzyloxy‐3‐methoxybenzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride (5 g) demonstrated the the best inhibition effects against cytosolic hCA II isoenzyme. On the other hand, 1,3‐Bis(4‐methylthiobenzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride, (5e) demonstrated the the best inhibition effects against AChE enzyme. The new imidazolinium, tetrahydropyrimidinium and tetrahydrodiazepinium salts were synthesized, spectroscopically characterized and crystal structure obtained in good yield by the reaction of the corresponding N,N’‐dialkylalkanediamine with triethyl orthoformate in the presence of ammonium chloride. The biological properties of all compounds were tested and the influence of ring size and benzylic N‐substituents on the biological activities were examined. The novel synthesised compounds were found as effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme.