Derivati N-benzil-3-amidokinuklidina kao inhibitori butirilkolinesteraze

Racemates as well as enantiomers of 3-amidoquinuclidine derivatives of acetic, pivalic, butyric and benzoic acid were prepared. Racemates and enantiomers of quaternary N-benzyl derivatives were synthesized as well by quaternization with benzyl bromide. Structures of all synthesized amides were established by spectroscopy (IR, MS, 1D and 2D NMR) and optical rotations measurements. Butyrylcholinesterase (BChE) was tested with a series of other enzymes as a possible biocatalyst in the hydrolysis of prepared racemic amides, but it was shown that hydrolysis did not occur. Taking into account this result and previously reported results on inhibitions of BChE by N-quaternary esters of quinuclidin-3-ol, N-benzyl amides were tested as possible inhibitors of BChE, as well. In experiments in which benzoylcholine was used as a substrate, it was shown that tested amides were inhibitors of BChE, the strongest of which was (S)-N-benzyl-3-benzamidoquinuclidinium bromide, (Ki=3.7 mikroM).