Substituted (Pyrroloamino)pyridines:  Potential Agents for the Treatment of Alzheimer's Disease

• Published in: Journal of medicinal chemistry Vol. 39; no. 2; pp. 582 - 587
• Main Authors: Davis, Larry, Klein, Joseph T, Kapples, Kevin J, Huger, Francis P, Smith, Craig P, Petko, Wayne W, Cornfeldt, Michael, Effland, Richard C
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 19-01-1996
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Animals; Biogenic Amines - antagonists & inhibitors; Biogenic Amines - metabolism; Biological and medical sciences; Cholinergic system; In Vitro Techniques; Medical sciences; Mice; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Pyridines - chemistry; Pyridines - pharmacology; Pyridines - therapeutic use; Quinuclidinyl Benzilate - antagonists & inhibitors; Quinuclidinyl Benzilate - metabolism; Rats; Structure-Activity Relationship; α2-Adrenergic receptor; Five membered ring; Rat; Alzheimer disease; Nitrogen heterocycle; Rodentia; In vitro; Organic hydrazine; Pyridine derivatives; Pyrrole derivatives; In vivo; Vertebrata; Mammalia; Structure activity relation; Mouse; Animal; Six membered ring; Affinity; Muscarinic receptor; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm950644v

A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure−activity relationships for this series is presented, along with the biological profiles of selected compounds.