Broad spectrum antiviral agents

Sieczkarski SB, Whittaker GR (2005) Viral entry, Curr Top Microbiol Immunol 285 1-23 Snell NJ (2001). Ribavirin-current status of a broad spectrum antiviral agent. Expert opinion on pharmacotherapy 2 1317-1324... 

The condensation of various heterocycles (pyrimidine or purine) with allyl bromide has been effected in the presence of KI. This selectively afforded N-1 isomers with pyrimidines, but N-9, N-3 or N-9, N-7 isomer mixtures with purines (88MIP1 89MI12 91 Mil). Alkyl esters of 3-adenin-9-yl-2-hydroxypropanoic acids were reported as broad-spectrum antiviral agents (85JMC282). 

Prusiner, P. and Sundaralingam, M. (1976). The crystal and molecular structures of two polymorphic crystalline forms of virazole (l-JS-D-ribofuranosyl-l,2,4-triazole-3-carboxamide). A new synthetic broad spectrum antiviral agent. Acta Crystallogr. B, 32, 419-26. [159]... 

Stapleton T, et al. Studies with a Broad Spectrum Antiviral Agent. International Congress and Symposium Series. London/New York Royal Society of Medicine Services, 1986. 

Adeninylhydroxypropanoic acid alkyl esters [(R,A)-AHPA esters, (30)] represent a new class of broad-spectrum antiviral agents, which are, like (5)-DHPA, targeted at SAH hydrolase (62). The free acid, (R,3)-AHPA, is only weakly active as an antiviral agent. Thus the alkyl moiety merely serves as a protecting group to facilitate uptake of AHPA by the cells. Within the cells, the AHPA alkyl esters would be hydrolyzed to release the free acid, which should then interact with SAH hydrolase. 

M. Hosoya, R. Snoeck, J. Neyts, G. Andrei, B. A. Murrer, B. Theobald, G. Bossard, G. Henson, M. Abrams, D. Picker Mechanism ofAnti-Human-lmmunodeficiency-Viras Action of Polyoxometalates, a Qass of Broad-Spectrum Antiviral Agents MoZ. Pharm. 42, 1109 (1992). 

HO OH ribavirin Viramid a broad-spectrum antiviral agent... 

Shuto S, Obara T, Toriya M, et al. New neplanocin analogues, I Synthesis of 6 -modified neplanocin A derivatives as broad-spectrum antiviral agents. J Med Chem. 1992 35 (2) 324-331. 

To cover adequately the advances made in the study of that apparently ideal, broad-spectrum antiviral agent interferon would require a whole review in itself. The topic has very recently been fully reviewed [96] and the reader is referred to this and to the earlier references to interferon [16-22]. 

The phosphonate acyclic nucleosides, 174-177 (Fig. 30), are broad spectrum antiviral agents active against DNA and retroviruses [207]. They are a family of structurally related compounds of which 175-177 show significant anti-HIV activity [208]. The mechanism of action of 175-177 remains to be elucidated. For the structurally related 174, it has been shown that it can, as such, be incorporated by the cells. Then, it is converted to the mono and diphosphoryl derivatives by cellular enzymes. The latter diphosphorylphosphonate, which can be considered as an analog of nucleoside-5 -triphosphate, may be the active form of the molecule, which inhibits viral DNA synthesis at concentrations which are by several orders of magnitude lower than those required for inhibition of cellular DNA synthesis. Similarly the anti-HIV activity of 175 may be attributed to a specific inhibition of the viral RNA-directed DNA synthesis. 

Fig. 30. Broad spectrum antiviral agents, phosphonate acyclic nucleosides...

Smith RA, Kirkpatrick W (eds) (1980) Ribavirin, A broad spectrum antiviral agent Academic, New York... 

Smith, R. and Kirkpatrick, W. (1980) Ribavirin, a Broad Spectrum Antiviral Agent, New York Academic Press. 

FIGURE 6 5-Alkynyl-l-beta-D-ribofuranosylimidazole-4-carboxamide 31 known as EICAR with broad-spectrum antiviral agent and pyrimido[l,6-fl]benzimidazole derivative 32 as potent anti-inflammatory-antimicrobial agent with analgesic activity [96]. 

E. De Clercq, 5-Adenosylhomocysteine hydrolase inhibitors as broad-spectrum antiviral agents, Biochem. Pharmacol. 36 2567 (1987). 

---