New antiarrhythmic agents. 2. Amide alkyl .alpha.-amino xylidides

Abstract

The synthesis of a series of N-alkyl 2-amino 2'',6''-xylidides is described. The method involved coupling of the N-alkyl-2'',6''-xylidine with the appropriate 2-haloacyl halide, followed by ammonolysis. Alternatively, alkylation of the 2-phthalimido 2'',6''-xylidide with NaH and the alkyl halide followed by hydrazinolysis was used. All compounds were evaluated for their ability to protect mice against chloroform-induced ventricular fibrillation. The compounds were generally more potent antifibrillatory agents than the corresponding secondary amides. All were more potent than tocainide and several showed less CNS toxicity. In dogs with ventricular arrhythmias resulting from myocardial infarction 5 compounds were tested. N-Ethyl-2-aminoaceto-4''-propoxy-2'',6''-xylidide was as potent as lidocaine and produced less CNS toxicity.