A series of thiophene and aryl substituted compounds 1a-f; 2a-b and 3a-c were synthesized by Erlenmeyer azolactone synthesis. These compounds were screened for antimicrobial activity method in vitro. Among the tested compounds 3c showed significant activity and some of the other compounds showed promising activity. The structure of new compounds synthesized during present investigation have been authentically established by their IR,1H NMR and Mass spectra and some QSAR studies. Key words: Thiophene; antimicrobial; antibacterial; antifungal.