Synthesis and muscarinic activity of 1,2,3,4-tetrahydropyrimidine derivatives.
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).
Jung
M H
MH
Korea Research Institute of Chemical Technology, P.O. Box 107, Yusong, Taejon 305-600, Korea.
Park
J G
JG
Yang
K J
KJ
Lee
M J
MJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects
D018721:Muscarinic Agonists; D011743:Pyrimidines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic