Synthesis and biological evaluation of 1,2,4 triazole and 1,3,4-Oxa-and Thiadiazoles derivatives

The alkaline hydrolysis with dimethylsulfate and potassium hydroxide of coumarin-6-derivatives [Ia-d] yielded 3-propenoic acid derivatives [IIa-d] which in turn were reached with thionyl chloride in toluene to give carbonyl chloride derivatives [IIa-d]. The latter compounds condensed with thiosemicarbazide in dioxane to give carbonylthiosemicarbazide derivatives [IVa-d], respectively. Cyclization of IVa-d, using sodium hydroxide yielded 5-mercapto- 1,2,4-triazol-3-yl-derivatives [Va-d]. Cyclodehydration of IVa-d using ortho-phosphoric acid or dicyclohexylcarbodiimide [DCC] led to the formation of the corresponding 5-amino-1,3,4-thia and oxadiazol-2-derivatives [VIa-d] and [VIIa-d], respectively. The antimicrobial and antiaflatoxigenic activities of Va-d, VIa-d were also evaluated

Pharmacological screening of few new 2-(substituted acetyl) amino-5-alkyl-1,3,4-oxadiazoles.

Nine new 2-(substituted acetyl) amino-5-alkyl-1,3,4-oxadiazoles were synthesised and confirmed on the basis of IR and nitrogen analysis. These were screened for spasmolytic, anti-inflammatory and their effects on blood pressure after determining ALD50. Compounds GK-4 i.e. 2-(diethylaminoacetyl)- amino-5-methyl-1,3,4-oxadiazole and GK-8 i.e. 2-(din-propylamino acetyl)-amino-5-ethyl-1,3,4-oxadiazole were found to be spasmolytic. Compound GK-6 i.e. 2-(diethylaminoacetyl)-amino-5-n-propyl-1,3,4-oxadiazole was found to be a potent hypotensive agent with the effect lasting for more than two hours.

Anticonvulsant and monoamine oxidase inhibitory activity of substituted oxadiazol-thiones.

Several 1,3,4-oxadiazol-thiones were synthesised and characterized by their melting points elemental analysis and I.R. spectra. All the oxadiazol-thiones possessed anticonvulsant activity which was reflected by protection upto 80% against pentylenetetrazole induced seizures and 40% protection against maximal electroshock induced seizures. Substantiations at position-3 of oxadiazol-thiones have shown marked effect on MAO inhibitory activity. No definite correlation between monoamine oxidase inhibitory and anticonvulsant activity could be established. It was observed that by the substitution of one, two and three methyl groups in the phenyl ring of 2-arylamino methyl side chain anticonvulsant activity against both maximal electroshock induced convulsions and pentylenetetrazol induced convulsions decreases i.e. the order of activity was found to be unsubstituted greater than monomethyl greater than dimethyl greater than trimethyl.