The present work, which has been undertaken is bonafide, for the synthesis of Novel substituted 1, 3, 4-thiadiazole derivatives. In this view we have made an attempt in reviewing the literature on 1, 3, 4-thiadiazole derivatives for their medicinal significance with the help of chemical abstract, journals and internet sites. In the light of above, the synthesis of N-substituted-{[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl] sulfanyl} 2-acetamide/2-propanamide/3-propanamide derivatives were established using literature survey. Nine new molecules were synthesized, with the standard chemicals and procedures. The synthesized compounds were tested for their preliminary tests, physical constants and TLC. The structures of the final products were confirmed employing spectral analysis such as IR, 1HNMR and Mass. The proposed compounds were screened for their anti-inflammatory activity with the standard drug. Compound 4b, 5a, 6c emerged as a potent anti inflammatory lead compounds.