2,4-diphenyl furan diamidines as novel anti-Pneumocytes carinii pneumonia agents

Dicationic 2,4-bis(4-amidinophenyl)furans 5-10 and 2,4-bis(4-amidinophenyl) -3,5-dimethylfurans 14 and 15 have been synthesized. Thermal melting studie s revealed high binding affinity of the compounds to poly(dA-dT) and to the duplex oligomer d(CGCGAATTCGCG)(2). All of the new compounds were effectiv e against Pneumocystis carinii pneumonia in the immunosuppressed rat model with up to 200-fold increase in activity compared to the control compound p entamidine. No toxicity was noted for 5, 7-10 at the dose of 10 mu mol/kg/d ; however, the isopropyl analogue 7 showed toxicity comparable to pentamidi ne at the dosage of 20 mu mol/kg/d. Dimethylation of the parent compound on the furan ring resulted in reduced activity and increased toxicity.