Synthesis, characterization and biological behavior of some Schiff's and Mannich base derivatives of Lamotrigine

Abstract

A series of various Schiff's and Mannich base derivatives (N1–2 & ND1–6) of Lamotrigine with isatin and substituted isatin were synthesized to get more potent anticonvulsant agents. The starting material for the synthesis of various new Schiff's and Mannich base derivatives was isatin (1H-indole- 2, 3-dione) which in turn was prepared from substituted isonitrosoacetanilide using aniline. Lamotrigine reacts with isatin & substituted isatin gave Schiff's bases (N1–2) which on reaction with various secondary amines (dimethylamine, diethylamine, morpholine) produced Mannich bases (ND1–6). The structures of newly synthesized compounds were characterized by using TLC, UV, FT-IR, 1HNMR and studied for their anticonvulsant activity. Anticonvulsant activity of all the derivatives was evaluated by MES method using phenobarbitone sodium & Lamotrigine as standard drugs and % reduction of time spent by animals in extension, flexion, clonus, and stupor phase were noted. Compounds ND-4 and ND-6 showed significant anticonvulsant activity when compared with that of standard drugs. The remaining all compounds show moderate activity. Biological activity data of the synthesized derivatives revealed that, the synthesized derivatives are good anticonvulsant agents as compared to Lamotrigine.

Keywords

• Lamotrigine
• Isatin
• Schiff's base
• Mannich base
• Anticonvulsant