Phosphonamidate Compounds for Butyrylcholinesterase Selective Inhibitors

摘要

To find a new type of cholinergic drug, phosphonamidate compounds 18-32 were synthesized using a click reaction between propargylated-9,10-Dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO, 2) and substituted benzyl azide. Their inhibitory activity against butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) was evaluated. Compound 31 was the most active of the 15 compounds (IC_(50) = 3.14 ± 0.02 μM for equine BuChE), whose IC_(50) value was slightly lower than the IC_(50) value of galantamine (IC_(50) = 9.4 ± 2.50 for equine BuChE).