Synthesis, antihistaminic action and theoretical studies of (4-methoxybenzyl)(1,4,5,6-tetrahydropirimidin-2-yl)amine hydroiodide

In this study, (4-methoxybenzyl)(1,4,5,6-tetrahydropyrimidin-2-yl)amine hydroiodide (2) was synthesized by reaction of 2-methylmercapto-1,4,5,6-tetrahydropyrimidine hydroiodide (1) and 4-methoxybenzylamine. The synthesized compound was tested for its in vitro H1-antihistaminic activity on guinea pig trachea. A promising bronchorelaxant effect of 2 was observed in histamine-contracted guinea pig tracheal chain via H1 receptor antagonism. In addition, the molecular geometry and gauge including atomic orbital (GIAO) 1H chemical shift values of the title compound in the ground state were calculated using the density functional method (DFT/UB3LYP) and Hartree–Fock (HF) approach using 6–311G+(d), 6–311G+(d,p), LANL2DZ, DGDZVP, and DGDZVP2 basis sets and compared with the experimental data. According to the experimental and theoretical results, HF/6–311G+(d) showed a better fit to experimental values in evaluating 1H-nuclear magnetic resonance (NMR) chemical shift values. Theoretical studies supported our findings, revealing the N12 atom as the most nucleophilic. In addition, other structures of the compound such as the aromatic ring and OCH3 group increased this property.