Synthesis of 2-aryl-4-(4-β-D-allopyranosyloxyphenyl)4,6,7,8-tetrahydroquinolin-5(1H)-one derivatives under solvent-free conditions and study of sedative activity
Under solvent-free conditions, syntheses of 2-aryl-4-(4-β-D-allopyranosyloxyphenyl)-4,6,7,8tetrahydroquinolin-5(1H)-one derivatives were carried out from chalcone (2a–2e), cyclohexane-1,3-dione (3), and NH4OAc in excellent yield without using any catalysts. The structure of the new compounds were characterized by 1H NMR, IR, and HR-MS spectroscopy. The preliminary bioassay tests of 4a–4j indicated that compounds 4b, 4e, and 4f exhibited potent sedative and hypnotic activity.
An improved synthesis of 2,2-disubstituted-1,2-dihydroquinolines and their conversion to 3-chloro-2,2-disubstituted-tetrahydroquinolines
Abstract N-(1,1-disubstitutedpropargyl)anilines can be cyclised to 2,2-disubstituted-1,2-dihydroquinolines by refluxing them in toluene containing cuprous chloride. Electron donating groups in the para position of the ring enhance the reaction rate and electron withdrawing groups markedly decrease the rate. The derived N-acetyldihydroquinolines can be cis dichlorinated and selectively monodechlorinated at the benzylic position to produce 3-chlorotetrahydroquinolines.
Is there a rationale for the use of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease?
Since the 1980s, the cholinergic hypothesis of the pathogenesis of Alzheimer's disease has proven to be a strong stimulus to pharmacological strategies aimed at correcting the cognitive deficit by manipulating cholinergic neurotransmission. Among these strategies, the one based on acetylcholinesterase inhibition is currently the most extensively developed for the therapy of Alzheimer's disease. The inhibitors' mechanisms of action are complex, including changes in the release of acetylcholine, and modulation of acetylcholine receptors. Various clinical trials of various inhibitors have shown that, on the whole, their effects were modest and, in the case of some drugs, were associated with frequent adverse reactions. Among the conceivable reasons for the limited efficacy of these drugs, those related to the pharmacological target deserve particular attention. This review, therefore, focuses on the complex nature of the acetylcholine system, the alterations of acetylcholinesterase and muscarinic receptor signal transduction in Alzheimer's disease, and the involvement of other neurotransmitters.