Synthesis of Reversible Inhibitors of Acetylcholinesterase (EC 3.1.1.7)

✍ Scribed by Peter Thanei-Wyss; Peter G. Waser

• Book ID: 102253111
• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: German
• Weight: 485 KB
• Volume: 66
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19830660731

✦ Synopsis

Abstract

The synthesis and characterization of some reversible acetylcholinesterase inhibitors are described in detail. They are structurally related to the natural substrate acetylcholine. All of them bear a trimethylammonium moiety as ‘cationic head’. Instead of an electrophilic ester group, the title compounds include a variety of functionalities, such as halide, ether, thioether, epoxide, amide, ketone and a double bond. The substances are thus suited as probes for the investigation of the esteratic subsite of the acetylcholinesterase active center.

Most of the synthesized compounds inhibit the enzyme in a competitive manner with inhibition constants in the range of 10^−5^ M to 10^−3^ M. With respect to acetylcholine (K~D~ ≤ 10^−5^ M and K~m~ = (1.6±0.5) 10^−4^ M) their affinity to acetylcholinesterase is in the same order of magnitude.