Human viral targets

Quartromicins are complex C2 symmetric macrocyclic natural products that have significant activity against a number of human viral targets.The diastereoselective synthesis of the endo- and exo-spirotetronate subunits of the quartromicins was accomplished by W.R. Roush and co-workers. The preparation of the exo-a-acetoxy aldehyde involved the Pummerer rearrangement oi a sulfoxide using acetic anhydride as the activating reagent and NaOAc as the co-catalyst. The yield of this transformation was modest and all attempts to improve its efficiency failed. 

Flohr, F., Schneider-Schaulies, S., Haller, O., and Kochs, G. (1999). The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures. FEES Lett. 463, 24-28. 

Abstract Acquired immunodeficiency syndrome (AIDS) and its related disorders, caused by retrovirus human immunodeficiency virus (HIV) are a major health concern worldwide. HIV protease is one of the major viral targets for the development of new chemotherapeutics. Currently, many HIV protease inhibitors are used in combination with HIV reverse transcriptase inhibitors. However, the use of current drugs regimens has several shortcomings, such as adherence, tolerability, long-term toxicity and drug- and... 

Russell DW, Hirata RK. Human gene targeting by viral vectors. Nat Genet 1998 18 325-330. 

Rossmann, M.G. Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus. Proc. Natl. Acad. Sci. USA, 85 4625-4627, 1988. 

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

The requirements of protease inhibitors as drugs in terms of potency, pharmacokinetics, and toxicity will vary depending on the nature of the infection and the goals of therapy. At one extreme is treatment of HlV-1, a chroific infection that requires life-long therapy and full suppression of viral replication. At the other extreme is the treatment of human rhinovirus (i.e., the cold virus), where short-term treatment to blunt viremia will likely be sufficient to reduce the unwanted symptoms of a cold. In all cases, viral proteases represent very attractive targets with familiar mechanisms of catalysis that frequently allow for the design of transition state analogs and with distinct specificities from host proteases. 

De Clercq E (1993) HlV-l-spedfic RT inhibitors highly selective inhibitors of human immunodeficiency virus type 1 that are specifically targeted at the viral reverse transcriptase. Med Res Rev 13 229-258... 

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