Synthesis, Antibacterial and Antifungal Activity of New 3-Aryl-5H-pyrrolo[1,2-a]imidazole and 5H-Imidazo[1,2-a]azepine Quaternary Salts

A series of novel 3-aryl-5<i>H</i>-pyrrolo[1,2-<i>a</i>]imidazole and 5<i>H</i>-imidazo[1,2-<i>a</i>]azepine quaternary salts were synthesized in 58-85% yields via the reaction of 3-aryl-6, 7-dihydro-5<i>H</i>-pyrrolo[1,2-<i>a</i>]imidazoles or 3-aryl-6,7,8,9-tetrahydro-5<i>H</i>-imidazo[1,2-<i>a</i>]azepines and various alkylating reagents. All compounds were characterized by ¹H NMR, ¹³C NMR, and LC-MS. The conducted screening studies of the in vitro antimicrobial activity of the new quaternary salts derivatives established that 15 of the 18 newly synthesized compounds show antibacterial and antifungal activity. Synthesized 3-(3,4-dichlorohenyl)-1-[(4-phenoxyphenylcarbamoyl)-methyl]-6,7-dihydro-5<i>H</i>-pyrrolo[1,2-<i>a</i>]imidazol-1-ium chloride <b>6c</b> possessed a broad activity spectrum towards <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, and <i>Cryptococcus neoformans,</i> with a high hemolytic activity against human red blood cells and cytotoxicity against <i>HEK-293</i>. However, compound <b>6c</b> is characterized by a low in vivo toxicity in mice (LD₅₀ > 2000 mg/kg).