Synthesis of p‐aminobenzamides of aminopiperidazines as potential antiarrhythmic agents

Abstract

Abstract1,2‐Dimethyl‐4‐aminopiperidazine (4), 1‐(2‐aminoethyl)2‐methylpiperidazine (11), 2‐(2‐aminoethyl)‐3‐meth‐yl‐2,3‐diazabicyclo[2.2.1]heptane (16), and 1,2‐dimethyl‐3‐aminomethylpiperidazine (21) have been synthesized. Amines 4, 11, and 16 were converted to the corresponding p‐nitrobenzamides 7,12, and 17. Catalytic reduction of the latter nitro derivatives gave the corresponding p‐aminobenzamides 8,13, and 18. For comparative studies, the acyclic analog, 4‐amino‐N[2‐(1,1,2‐trimethylhydrazino)ethyl]benzamide (25) was also synthesized. Compounds 8,13 and 25 which are analogs of procainamide were evaluated in the isolated cardiac Purkinje fiber preparation by measuring their effects on the action potential upstroke velocity.