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.