Muscarinic receptor 1 agonist activity of novel N-aryl carboxamide substituted 3-morpholino arecoline derivatives in Alzheimer's presenile dementia models

Earlier we have reported the effect of arecoline thiazolidinone and morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's presenile dementia models. To elucidate further our Structure-Activity Relationship (SAR) studies on the chemistry and muscarinic receptor 1 binding efficacy, a series of novel carboxamide derivatives of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl) morpholine molecule have been designed and synthesized as a new class of M1 receptor agonists with a low toxicity effect pro. le that enhances memory function in animal models of Alzheimer's presenile dementia and also modulates the APP secretion from rat brain cerebrocortical slices by activating M1 receptor in vitro. Results suggest that compound 9b having methyl group at the para position of the aryl group attached to the carboxamide of morpholino arecoline could emerge as a potent molecule having antidementia activity. (C) 2009 Published by Elsevier Ltd