The (2-butyl -5-amino-3-benzofuranyl) 4-methoxy phenyl methanone heterocyclic and isoxazolic acids have been synthesized by the reaction of (2-butyl -5-amino-3-benzofuranyl) 4-methoxy phenyl methanone with different heterocyclic and isoxazolic acids were described (DBMY20-28). All the compounds were synthesized by conventional method and characterized by IR, 1H NMR and mass spectral data. The synthesized compounds were tested for antimicrobial activity against Staphylococcus aureus, Escherichia coli and pseudomonas aeruginosa. Among the synthesized compounds (2-butyl -5-amino-3-benzofuranyl) 4-methoxy phenyl methanone acids (DBMY-22,27,28) was found the most active derivative against S. aureus, E. coli and P. aeruginosa and The compounds DBMY-22, 27, 28 was found the most active derivative against Candida albicans and Asperigillus fumigatus respectively. The other Compounds exhibited moderate activity against the other test microorganisms.