Triazine anticonvulsants

Reaction of 2,3-dichlorobenzoyl chloride with cyanide ion leads to the corresponding benzoyl cyanide (141). Condensation of that reactive intermediate with aminoguanidine 142 leads to the hydrazone-like product 143. Treatment with base results in addition of one of the guanidine amino groups to the nitrile function and formation of the 1,2,4-triazine ring. The product, lamo-trigine (144), is described as an anticonvulsant agent [31]. 

Imidazo[4,S-J]l,2,3-triazines and pyrazolo[3,4-Similar reactions have been used to obtain imidazopytidazines <95JHC1417, 1423 >. 

Preparation of the anticonvulsant agent lamotigrine (91-3) illustrates an alternate approach to 1,2,4-triazines. Condensation of acyl cyanide (91-1) with dicyanamide gives imine (91-2) as the initial product. Treatment of that intermediate with a base leads to the addition of the guanidino anion to the nitrile and thus the formation of the triazine ring [92]. 

The 1,2,4-triazine system is a constituent of antibiotics of the pyrimido[5,4-c][l,2,4]triazine-5,7-dione type, e.g. planomycin 29. Lamotrigine 30, a sodium channel blocker, is clinically used as anticonvulsant. 

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