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Synthesis and muscarinic activity of 1,2,3,4-tetrahydropyrimidine derivatives
1Korea Research Institute of Chemical Technology, P.O. Box 107, Yusong, Taejon 305-600, Korea.
Abstract:
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).
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