Novel Piperidinium and Pyridinium Agents as Water-Soluble Acetylcholinesterase Inhibitors for the Reversal of Neuromuscular Blockade

The synthesis of novel pyridinium salts as powerful acetylcholinesterase inhibitors with improved water solubility is reported, for example 43 (IC 50=0.007 μM, 50 mg/mL). A series of piperidinium and pyridinium agents containing a common structural fragment of 5,6-dimethoxybenzothiophene have been synthesised as water-soluble acetylcholinesterase inhibitors. Several compounds, for example 42 (AChE IC 50 0.03 μM) have been found to reverse the neuromuscular blockade induced by vecuronium bromide in vitro and in vivo. Coupled with their high water solubility (up to 30–60 mg/mL), these compounds are potentially useful as intravenous reversal agents of neuromuscular blocking agents in surgical anaesthesia.