The synthesis and anticonvulsant activity of a series of 2-aryl-5-hydrazino-1,3,4-thiadiazoles are described. The combination of preferred aromatic substituents in the 2-position coupled with alkyl substitution on the hydrazine moiety led to a number of potent compounds lacking sedation, ataxia, or lethality. 5-(2-Biphenylyl)-2-(1-methylhydrazino)-1,3,4-thiadiazole (4m) represents a new class of anticonvulsant agent and compares favorably with the standard drugs phenytoin, phenobarbital, and carbamazepine.

Two different structural types of 2-aryl-1,3,4-thiadiazole amidines were synthesized and evaluated for anticonvulsant activity. Enhancement of the inherent anticonvulsant activity therein and separation of this activity from the accompanying sedative action of these compounds were attempted. The most potent compounds occurred in the 2-(trifluoromethyl)phenyl series of type 3 amidines, but they also possessed a relatively high level of neurotoxicity and sedation as demonstrated in the rotorod test.

The synthesis and anticonvulsant activity of a number of 2-aryl-5-guanidino-1,3,4 thiadiazoles are described. The unsubstituted guanidine 2a was found to possess potent anticonvulsant properties; considerable reduction or loss of activity however was observed with the majority of the substituted guanidines. Incorporation of the guanidine group into an imidazoline ring also resulted in a loss of activity. Secondary pharmacological evaluation confirmed the anticonvulsant properties of 2a but also revealed that the compound exhibited a considerable degree of sedative activity.

Application of the principles of synthesis design to the problem of prostaglandins led to many possible routes, including one commencing with endo-dicyclopentadiene. This starting material was then converted into racemic prostaglandin FZa in a minimum of ten stages via bicyclo [3.3.0]octane intermediates.

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