对称的奎宁环类和托品类双季铵和多季铵化合物的合成及其神经肌肉阻断作用

本文报道22个奎宁环类和托品类双季铵和多季铵化合物的合成及其对膈肌膈神经标本的抑制作用。初步试验表明,带有草酰胺链的化合物较其他链—(CH₂)₆—或—CH₂OCH₂—]的好。通过这两类化合物的构效分析,看出化合物中即便具有神经节阻断剂作用的短链(3,6或8个原子),但如在分子的氨基部分以较庞大的环状基团奎宁环或托品(分别带有适当取代基)替代成为大季铵头时,则转化为神经肌肉阻断作用。

STUDIES ON THE SYNTHESIS AND NEUROMUSCULAR BLOCKING ACTIVITY OF SYMMETRICAL BIS-AND POLY-QUATERNARY DERIVATIVES OF QUINUCLIDINE AND TROPINE

In order to search for new muscle relaxants, twenty-two new compounds of symmetrical bis-and poly-quaternary derivatives of quinuclidine and tropine were prepared by reaction of tertiary amines with 1,6-dibromohexane or 1,1'-dichloromethyl ether, and reaction of oxamides with o-chloro benzyl chloride or N-(chloromethoxymethyl)-2-hydroxyiminomethyl pyridinum chloride.The compounds with short central chains (3 or 6 atoms), usually conductive to ganglion blocking activity, became neuromuscular blocking activity when the simple terminal amino groups were replaced by bulkier quinuclidine or tropine groups. This was also true for the oxamides with 8-atom chains.Preliminary pharmacological tests revealed that these compounds with oxamide chain exhibited stronger blocking effect than the others.