Design of Anti-Viral Agents Other than Nucleoside Analogues

Abstract

It is generally accepted that, by the very nature of the invading organisms and their interactions with the host, the search for anti-viral compounds is going to be much more difficult than the corresponding searches for anti-bacterial and anti-fungal substances. Having accepted this situation it is interesting to note that over the past ten years the only compounds to emerge as serious contenders for a place as commercially important anti-bacterials are more β-lactams (e.g. thienamycin, aztrenonam) and more nalidixic acid analogues (e.g. ofloxacin). The situation with regard to the establishment of new anti-fungal agents is even simpler; only imidazole derivatives (e.g. fluconazole) related to ketoconazole have emerged as compounds that may take up a noteworthy position in the market place. Not surprisingly, therefore, the establishment of promising anti-viral agents over the same time period has been painfully slow. Nevertheless acyclovir and various prodrugs, as well as some other nucleoside analogues with potent anti-viral properties, have been discovered and will be discussed in other Chapters. The opportunities afforded by inhibiting virally-coded enzymes with nucleoside analogues are well recognised and a number of interesting anti-viral agents have been ‘designed’ using the information (viz. mode of action, metabolism, etc.) gained from the leading compounds.