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

Abstract

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) H-1 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 H-1-nuclear magnetic resonance (NMR) chemical shift values. Theoretical studies supported our findings, revealing the N-12 atom as the most nucleophilic. In addition, other structures of the compound such as the aromatic ring and OCH3 group increased this property.