A 50-compound library based on the marine natural product oroidin was synthesized and assayed for anti-biofilm activity against PAO1 and PA14, two strains of the medically relevant gamma-proteobacterium Pseudomonas aeruginosa. Through structure-activity relationship (SAR) analysis of analogues based on the oroidin template, several conclusions can be drawn as to what structural properties of the synthetic derivatives are necessary to elicit a biological response. Notably, the most active analogues identified were those that contained a 2-aminoimidazole (2-AI) motif and a dibrominated pyrrolecarboxamide subunit. Here we disclose the synthesis and subsequently determined biological activity of this unique class of compounds as inhibitors of biofilm formation that have no direct antibiotic effect.