Effect of novel N-arylurea- substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer’s dementia models

The cholinergic hypothesis of Alzheimer’s disease has spurred the development of numerous compounds aimed at increasing central cholinergic neurotransmission. Symptomatic treatment can be given by cholinomimetics with the pharmacological profile of muscarinic receptor 1 (M1 receptor) agonist and/or acetylcholineesterase (AChE) inhibitors. Novel bioactive six-membered N-arylureasubstituted 3-morpholino arecoline derivatives were synthesized by N-benzyl aminoethanol coupling with α-bromoacetylpyridine followed by reduction and cyclization. Five of the derivatives showed high M1 receptor binding affinity in vitro and elicited beneficial effects in in vivo memory and learning models in rats.