Synthesis and anticonvulsant activity of some novel 3‐aminoquinazolines

A number of novel 3‐aminoquinazolines were obtained via two synthetic pathways. In the first method o‐aminobenzoylhydrazines were prepared either by reacting an isatoic anhydride and a hydrazine or by reacting o‐nitrobenzoic acid with a hydrazine, followed by catalytic reduction. Subsequent cyclization with an appropriate orthoester provided 3‐aminoquinazolines and 2‐methyl‐3‐aminoquinazolines. The second pathway involved condensation of o‐aminoacetophenone with a hydrazine to form hydrazones which were reduced to aminohydrazines and cyclized as above to yield 4‐methyl‐3‐aminoquinazolines and 2,4‐dimethyl‐3‐aminoquinazolines. The title compounds were evaluated in mice in MES and sc Met seizure models for anticonvulsant activity, and in the rotorod test for neurotoxicity. They were generally toxic. However, 4‐methyl‐3‐(N‐piperidino)‐3,4‐dihydroquinazoline hydrochloride exhibited activity comparable to that of methaqualone.