2,4-Diphenyl furan diamidines as novel anti-Pneumocystis carinii pneumonia agents.

Abstract

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 studies 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 effective against Pneumocystis carinii pneumonia in the immunosuppressed rat model with up to 200-fold increase in activity compared to the control compound pentamidine. No toxicity was noted for 5, 7-10 at the dose of 10 micromol/kg/d; however, the isopropyl analogue 7 showed toxicity comparable to pentamidine at the dosage of 20 micromol/kg/d. Dimethylation of the parent compound on the furan ring resulted in reduced activity and increased toxicity.

• Authors: I Francesconi, W D Wilson, F A Tanious, J E Hall, B C Bender, R R Tidwell, D McCurdy, D W Boykin
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 42 Issue 12 Pg. 2260-5 (Jun 17 1999) ISSN: 0022-2623 [Print] United States
• PMID: 10377232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amidines
• Antifungal Agents
• Furans
• DNA

Topics

• Amidines (chemical synthesis, chemistry, pharmacology, toxicity)
• Animals
• Antifungal Agents (chemical synthesis, chemistry, pharmacology, toxicity)
• DNA (chemistry)
• Furans (chemical synthesis, chemistry, pharmacology, toxicity)
• Immunocompromised Host
• Pneumonia, Pneumocystis (drug therapy)
• Rats
• Structure-Activity Relationship