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

Abstract	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 profile 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.
Authors	Manish Malviya, Y C Sunil Kumar, R B Mythri, C Venkateshappa, M N Subhash, K S Rangappa
Journal	Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 17 Issue 15 Pg. 5526-34 (Aug 01 2009) ISSN: 1464-3391 [Electronic] England
PMID	19595599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Amyloid beta-Protein Precursor Morpholines Muscarinic Agonists Receptor, Muscarinic M1 Arecoline Inositol 1,4,5-Trisphosphate morpholine
Topics	Alzheimer Disease (drug therapy) Amyloid beta-Protein Precursor (metabolism) Animals Arecoline (chemical synthesis, chemistry, pharmacology, therapeutic use) Cerebral Cortex (drug effects, metabolism) Dose-Response Relationship, Drug Humans Inositol 1,4,5-Trisphosphate (metabolism) Male Maze Learning (drug effects) Memory Disorders (chemically induced, drug therapy) Morpholines (chemical synthesis, chemistry, pharmacology, therapeutic use) Muscarinic Agonists (chemical synthesis, chemistry, pharmacology, therapeutic use) Protein Binding Rats Rats, Wistar Receptor, Muscarinic M1 (agonists, metabolism) Structure-Activity Relationship

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