Herein, we report the synthesis and the screening results of the unique acyl imidazopyrimidinyl and acyl imidazolyl structural analogues of oroidin as inhibitors of biofilm formation that have minimal or no microbicidal effect. A focused library based on the marine natural product oroidin scaffold was synthesized and assayed for antibacterial and anti-biofilm activity against medically relevant bacterial pathogens. Based on the structure–activity relationship (SAR) it is concluded that the most active analogues are those that contained a 2-aminoimidazole motif and brominated pyrrolecarboxamide subunit with carbonyl functionality in the side chain.