Abstract: This work involves to synthesisnovel organic compounds and studies their pharmacological. Approach: The title compound quinazolinone derivatives were prepared by reacting 3 amino of 3-amino-2-methylquinazolin-4(3H)-one (first) with various aldehydes and ketones, and second coupling through diazonium salts with resorcinol or with ethylacetoacetate then cyclized with hydrazine. The starting material 3-amino-2-methylquinazolin-4(3H)-one was synthesized by reacting hydrazine with 2-methyl-4H-benzo[d][1,3]oxazin-4-one, which in turn was prepared from anthranilic acid. The chemical structures of the synthesized compounds were confirmed on the basis of their spectral data (FT-IR, UV/visible, ¹HNMR, spectra and CHN analyss). All synthesized compounds were tested in vitro against a number of microorganisms (Staphylococcus aurous, E.coli, Proteus vulgaris, Pseudomonas, and Klebsiella) and two fungal Aspergillus niger and Candida albicans in order to assess their antimicrobial properties. Results: The study indicates that these compunds have high activity against tested bacteria. Aim: We aim to synthesize quinazolinone derivatives having active moieties to evaluate their antimicrobial activities. Conclusion/Recommendations: Based on the reported results, it may be concluded that 3-amino-2-methyl- quinazolin-3(4H)-one act as synthones for Schiff bases and for diazonium coupling. [Researcher 2010;2(4):82-88]. (ISSN: 1553-9865).