In the present study, a new series of benzofuran-integrated 1,3,4-thiadiazoles were prepared starting from pyrazol-4-carboxaldehyde derivatives 3a,b. Thus, reaction of compound 3a,b with benzyl hydrazine carbodithioate afforded hydrazine carbodithioate derivatives 4a,b. Treatment of compound 4a with hydrazonoyl halides 5e,f afforded 1,3,4-thiadiazoles 6a, b while the reaction of 4b with hydrazonoyl halides 5a-d yielded 1,3,4-thiadiazoles 7a,b. on the other hand, new pyridine derivatives can be synthesized via the reaction from the reaction of chalcone 8 with different C-nucleophile such as ethyl acetoacetate, benzoyl acetonitrile or acetyl acetone. All the new derivatives were characterized by spectral data. Some of the newly prepared compounds were investigated against different pathogenic microbes. The results of the antimicrobial activity revealed that all the tested compounds showed no activity except compound 6a which showed weak activity against all tested microorganisms. Compound 6b was weak active against B. subtilis and compound 7c was intermediate active against E. coli.