A series of 3-amino-3-methyloxindoles was synthesized from indoles by modification of previously described procedures. All compounds showed activity against chloroform-induced arrhythmias in mice. One member of the series, 3-methyl-3-piperidinooxindole, displayed activity equal to that of lidocaine while showing only one-third the acute toxicity.
Keyphrases 3-Amino-3-methyloxindoles-synthesis, antiarrhythmic activity, compared to lidocaine 0 Antiarrhythmic activity-3-amino-3-methyloxindoles synthesized and screened
The authors' interest in the synthesis and pharmacological evaluation of lidocaine (I) analogs goes back several years, and initially attention was focused on compounds where the basic group was a hydrazine derivative (1). Recent work in these laboratories on the chemistry of aminooxindoles (2) has led to an expansion of this interest and to the present report concerning the synthesis and antiarrhythmic activity of a series of 3-amino-3-methyloxindoles (11).
Examination of I1 showed that these compounds incorporate the principal structural moieties of the local anesthetic and antiarrhythmic drug lidocaineuiz., an aromatic nucleus, an amide linkage, and a basic amino group, in a nearly rigid framework. Closer examination revealed that the title compounds possess unique structural features that set them apart from lidocaine and its many congeners. Significant differences can be discerned in the stereochemistry of I1 and lidocaine. Thus, I1 has the cis-amide configuration, while the protonated form of lidocaine, (8) T. B.