Synthesis and Antiallergy Activity of [1,3,4]Thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one Derivatives. I

A series of 6-substituted [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives 4a-z were synthesized from 5-substituted 1,3,4-thiadiazol-2-amines 5 by the following consecutive reactions : pyrimidine ring closure with bis(2,4,6-trichlorophenyl)malonate, nitration, chlorination, amination, hydrogenation and diazotization. The structure of 4 was confirmed by an alternate synthesis of 4,involving reaction of 5-subsituted 2-azido-1,3,4-thiadiazole 13 with ethyl cyanoacetate, followed by the Dimroth rearrangement and ring closure.The antiallergic activities (anti-passive peritoneal anaphylaxis, anti-passive cutaneous anaphylaxis and anti-slow reacting substance of anaphylaxis activities) of the products were evaluated.