Patent Evaluation: Trisubstituted tetrahydrofuran antifungal agents

Summary

Novelty: Novel tri-substituted tetrahydrofurans, stated to have potential utility as antifungal agents, are disclosed.

Biology: A range of in vivo rodent studies demonstrating pharmacological efficacy are presented. These include evaluation of antifungal activity using an Aspergillus pulmonary infection model. Oral treatment (100mg/kg/day) was initiated 24 hours post-infection and maintained for 4 days. A preferred test compound was found to have greater antifungal activity than itraconazole, fluconazole and saperconazole. Results are presented in figures.

Chemistry:(-)-[(5R)-cis]-4-[4-[4-[4-[[5-(2-4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl) tetrahydofuran-3-yl]methoxy]phenyl-1-piperazinyl]phenyl]-2,4-dihydro-2[(S)-(1-methylpropyl)]-3H-1,2,4,-triazol-3-one is one of thirty compounds specifically exemplified. Full preparative details using standard techniques are presented.