Synthesis, local anaesthetic and antiarrhythmic activities of N-alkyl derivatives of proline anilides

We describe here the design, synthesis and evaluation of in vivo local anaesthetic and antiarrhythmic activities of a series of N-alkylproline anilides. Most of the compounds demonstrated surface anaesthetic activity higher than that of lidocaine, ropivacaine and bupivacaine. We established that the local anaesthetic activity was sensitive to structural variations in the substitution pattern at the aromatic ring and the type of alkyl group at the proline nitrogen atom. Some of the prepared N-alkylproline anilides possessed significant antiarrhythmic activity with higher therapeutic indexes than the reference drugs.

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► A series of new N-alkylproline anilides was synthesized.
► They demonstrated high surface and infiltration local anaesthetic activity.
► Significant antiarrhythmic activity was observed.
► The structure–activity relationship in the series was discussed.
► The lead compounds showed therapeutic indexes higher than that of the reference drugs.