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Acyclic Phosphonomethylether Nucleosideinhibitors Of Respiratory Viruses, Dale L. Barnard, N. Bischofberger, C. U. Kim, J. H. Huffman, R. W. Sidwell, J. P. Dougherty, W. Lew, M. A. Williams, W. Yang
Acyclic Phosphonomethylether Nucleosideinhibitors Of Respiratory Viruses, Dale L. Barnard, N. Bischofberger, C. U. Kim, J. H. Huffman, R. W. Sidwell, J. P. Dougherty, W. Lew, M. A. Williams, W. Yang
Animal, Dairy, and Veterinary Science Faculty Publications
A series of acyclic phosphonomethylether nucleosides were synthesized and then evaluated for inhibitory activity against respiratory viruses of clinical significance using CPE inhibition, neutral red uptake and virus yield reduction assays. Of the 20 compounds synthesized, none significantly inhibited influenza A or B viruses or respiratory syncytial virus strains A2, Long or 18537; the selective indices (SI) were less than 10. A new compound, GS-2128 (2R, 5R-9-[2,5-dihydro-5-(phosphonomethoxy)-2-furanyl]adenine; D4API), selectively inhibited adenovirus 5 (SI>10) as did GS-0577 (9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine; HPMPA) and GS-0504 [(S)-1-[3-hydroxy-2-(phosphonylmethoxypropyl)]-cytosine; HPMPC]. The 50% effective concentrations (EC50) ranged from 8-100 μg mL-1 and 50% cell inhibitory concentrations (CC50) from …