Synthesis and muscarinic activity of 1,2,3,4-tetrahydropyrimidine derivatives

Article abstract of DOI:10.1002/1521-4184(200103)334:3<79::AID-ARDP79>3.0.CO;2-7

3-Methyl-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde O-substituted oximes 4 and 1-(3-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)ethanone O-substituted oximes 9 have been prepared as bioisosteric congeners of arecoline which is a muscarinic agonist for treatment of Alzheimer's disease. Starting from pyrimidine-5-carbaldehyde 1, formation of the 3-methylpyrimidinium salt and subsequent reduction afforded 1,2,3,4-tetrahydropyrimidine derivatives which were converted into oxalate salts in the interest of purity and stability. Binding affinities of prepared compounds for the cloned human muscarinic M₁ receptor (h-M₁) were determined by radioligand binding assay using [³H]-N-methylscopolamine (NMS).