Reference

Antiviral compositions

Antiviral compositions. Horrobin, David Frederick (Can. ). Eur. Pat. Appl. EP 135312 A2 27 Mar 1985,7 pp. DESIGNATED STATES: R: AT, BE, CH, DE, FR, GB, IT, LI, LU, NL, SE. (English). (European Patent Organization). CODEN: EPXXDW. CLASS: ICM: A61K031-52. ICS: A61K031-70; A61K045-02. ICI: A61K031-52, A61K031-19; A61K031-70, A61K031-19; A61K031-52, A61K033-14; A61K045-02, A61K031-19. APPLICATION: EP 84-305102 26 Jul 1984. PRIORITY: GB 83-20203 27 Jul 1983. DOCUMENT TYPE: Patent CA Section: 63 (Pharmaceuticals) The antiviral effectiveness of such antiviral agents as acyclovir [59277-89-3], idoxuridine [54-42-2], vidarabine [5536-17-4], etc., was enhanced by formulating with a physiol. active Li salt. Viruses do not become resistant to the Li compds. E.g., an ointment contained acyclovir 5, Li succinate [16090-09-8] 8, and lanolin base 87%.

Metabolic activation of the nucleoside analog 9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}guanine in human diploid fibroblasts infected with human cytomegalovirus

Metabolic activation of the nucleoside analog 9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}guanine in human diploid fibroblasts infected with human cytomegalovirus. Biron, Karen K.; Stanat, Sylvia C.; Sorrell, Jann B.; Fyfe, James A.; Keller, Paul M.; Lambe, Catherine U.; Nelson, Donald J. (Dep. Virol., Wellcome Res. Lab., Research Triangle Park, NC 27709, USA). Proc. Natl. Acad. Sci. U. S. A., 82(8), 2473-7 (English) 1985. CODEN: PNASA6. ISSN: 0027-8424. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) BW B759U [9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}guanidine] [82410-32-0] is a more potent inhibitor of human cytomegalovirus (HCMV) in vitro than is the related nucleoside analog acyclovir (ACV) [59277-89-3]. BW B759U was selectively activated to the 5'-triphosphate (BW B759U-triphosphate [86761-38-8]) in those measured for ACV-triphosphate [66341-18-2] and up to as much as 100-fold higher than the levels found in uninfected cells. BW B759U-triphosphate accumulated in HCMV-infected cells with time; the rate of this increase was dependent upon the drug dose and virus multiplicity of infection. Enzyme activities that catalyzed the phosphorylation of thymidine and 2'-deoxycytidine increased 3- to 7-fold in exts. of cells early after HCMV infection but thereafter declined. No concomitant increase in the rate of BW B759U phosphorylation was detected under these assay conditions. Maximal rate of accumulation of both BW B759U-triphosphate and ACV-triphosphate after a short exposure to drug occurred in the late phase of the infective cycle, as the titer of extracellular virus reached a peak in untreated cultures, but after the decline of stimulated host deoxypyrimidine kinase activities. Once formed, the BW B759U-triphosphate pool decreased very slowly and thus it persisted for several days in both HCMV-infected and uninfected cells.