Document Type
Article
Journal/Book Title/Conference
Acyclic phosphonomethylether nucleosideinhibitors of respiratory viruses
Volume
8
Issue
3
Publisher
International Medical Press
Publication Date
1997
First Page
223
Last Page
233
Abstract
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 40-1000 μg mL-1. All three compounds were also found to be active against laboratory strains and clinical isolates of adenovirus types 1, 2, 8 and 41 with EC50 values ranging from 0.2 to 10 μg mL-1. Two compounds, GS-438 (9-(2-phosphonylmethoxyethyl)guanine, PMEG) and GS-2542 (9-[3-phosphonomethoxy)methoxymethyl]guanine) inhibited parainfluenza virus 3 strain C243, with SI of 52 and >333, respectively, PMEG also inhibited measles virus strains CC, Halonen and Chicago with EC50 values ranging from 0.03-9 μg mL-1. These data suggest that these compounds should be considered for possible development as therapeutic agents for respiratory virus infections.
Recommended Citation
Barnard, D.L., N. Bischofberger, C.U. Kim, J.H. Huffman, R.W. Sidwell, J.P. Dougherty, W. Lew, M.A. Williams, W. Yang. 1997. Acyclic phosphonomethylether nucleoside inhibitors of respiratory viruses. Antiviral Chem. Chemother. 8: 223-233.
Comments
Published by the International Medical Press in the Journal of Antiviral Chemistry & Chemotherapy.
The Journal can be accessed by clicking the link below:
http://www.intmedpress.com/index.cfm?pid=16