In accordance with the present invention, a novel class of substituted aryl compounds (containing ether, ester, amide, ketone or thioether substitution) that promote the release of ligands involved in neurotransmission have been discovered. In a particular aspect, compounds of the present invention are capable of modulating acetylcholine receptors. The compounds of the present invention are capable of displacing one or more acetylcholine receptor ligands, e.g., <3>H-nicotine, from mammalian neuronal membrane binding sites. Invention compounds may act as agonists, partial agonists, antagonists or allosteric modulators of acetylcholine receptors. Therapeutic indications for compounds with activity at acetylcholine receptors include diseases of the central nervous system such as Alzheimer's disease and other diseases involving memory loss and/or dementia (including AIDS dementia); cognitive dysfunction (including disorders of attention, focus and concentration), disorders of extrapyramidal motor function such as Parkinson's disease, progressive supramuscular palsy, Huntington's disease, Gilles de la Tourette syndrome and tardive dyskinesia; mood and emotional disorders such as depression, anxiety and psychosis; substance abuse including withdrawal symptoms and substitution therapy; neurocrine disorders and dysregulation of food intake, including bulimia and anorexia; disorders or nociception and control of pain; autonomic disorders including dysfunction of gastrointestinal motility and function such as inflammatory bowel disease, irritable bowel syndrome, diarrhea, constipation, gastric acid secretion and ulcers; pheochromocytoma, cardiovascular dysfunction including hypertension and cardiac arrhythmias, as well as co-medication uses in surgical applications.
NOVEL SUBSTITUTED ARYL COMPOUNDS USEFUL AS MODULATORS OF ACETYLCHOLINE RECEPTORS