We describe here an easy and efficient method to obtain S-alkylated derivatives of thio-quinazolinone using different alkylating agents via a solvent-free microwave-assisted method. The alkylated thio quinazolinones were further sequentially condensed with hydrazine hydrate and different aromatic aldehydes to get the hydrazones, which were studied for QSAR. The synthesized compounds were subjected to a prediction of biological activities. A software application (PASS) was used for this purpose. The relationship between structure and different biological activities was studied and the different derivatives were recommended for the screening of some specific activities like anti-tuberculosic, anti-mycobacterial and HDL cholesterol increasing activities.