Abstract: New paracetamol derivatives and their N-substituted acyclic nucleoside analogues were prepared. The synthesized compounds were tested for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, micrococcus,salmonella typhi and salmonella para typhi.The synthesized compounds were tested also against fungi species such as aspergillus flavus, aspergillus fumigates, aspergillus ochraceus and candida albicans. Most of tested compounds exhibited moderate to high antimicrobial activity while few compounds were found to exhibit little or no activity against the tested microorganisms.