N-Substituted 1H-Pyrimidin-4-One Derivatives Possessing Anxiolytic Activity

Abstract

The logical framework approach was implemented for designing CNS-active N-substituted 1H-pyrimidin-4-ones. Formation energies of possible ligand—receptor complexes with D₂-dopamine and GABA_A Receptors were determined from molecular docking calculations. The results allowed the probability of psychotropic activity manifesting in the modeled compounds to be estimated. The most promising compounds were prepared by a modified synthetic procedure. The effect of the heteroatom type in N-heterocyclic 1H-pyrimidin-4-ones on the product yield was studied. Compounds I – IV and VI at a dose of 50 mg/kg exhibited anticonflict activity. The mercaptotriazole derivative of pyrimidin-4-one had the greatest anticonflict activity.