BACKGROUND OF THE INVENTION 1. Field of the Invention. The present invention relates to antiviral molecules. In particular, the invention relates to an oral therapeutic which uses a TZV molecule which is potent and safe in in vitro assays.

Viruses cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections in particular are currently limited, as are drugs to combat Ebola, Dengue fever, and other infections. The TZV molecule has been shown experimentally to provide some potency against influenza and other viral infections.

BRIEF DESCRIPTION OF THE DRAWINGS

Various other objects, features, and attendant advantages of the present invention will become more fully appreciated as the same becomes better understood when considered with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the several views, and wherein:

Fig. 1 shows the molecule of the present invention.

Novel Azolo-l,2,4-Triazine Derived Antivaral Oral Therapeutic

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

15

Efficient methods for the incorporation of N-isotope into l,2,4-triazolo[5,l-c][l,2,4]triazines have been developed. Some of these methods and the resulting molecules are shown in Russian Patent number 2294936 which is herein incorporated by reference. The label can be selectively introduced into either the azolo or azine fragment of the molecule.

Stable isotope labeling provides valuable information on the structure of a molecule and is often used in studies of reaction mechanisms of rearrangements and transformations in heterocyclic

1-4

compounds. Incorporation of stable isotopes into the molecules of biological active compounds can

5-8

be used in pharmacological studies on early phases of drug design . It substitutes the use of

5,8 radioactive isotopes and allows the investigation of drug metabolism to be carried out in humans. The great interest in l,2,4-triazolo[5,l-c][l,2,4]triazinones and their sodium salts, along with azoloannelated 1,2,4-triazines, is due to their high activity against different kinds of viruses including

9- influenza and bird flu (culture H5N1).

One general method for the synthesis of l,2,4-triazolo[5,l-c][l,2,4]triazines and related azolo fused 1 ,2,4-triazines is based on the reaction of diazoazoles with CH-active methylene

15

compounds. The use of N-labeled nitrous acid for diazotation of 2-aminoimidazole

15 followed by coupling with Meldrum's acid results in imidazo[2,l-c][l,2,4]triazinone containing N

1

isotope in azine cycle. So, diazoazoles 2a*,b* were obtained by treatment of 2-R-amino- 1,2,4-

15

triazole la,b with K NO^ (86% of label) under acidic conditions. Reaction of 2a*,b* with ethyl nitroacetate as active methylene compound in the presence of Na^CO^ gave salts 4a*,b* (Scheme 1).

This results in formation of a mixture of potassium and sodium salts which is acidified to give azoloazines 5a*,b* and then converted exclusively to sodium salt 4a*,b* by treatment with a solution of sodium carbonate.

A problem observed with prior attempts to use TZV as an effective anti-viral agent has been toxicity. The molecule shown below and in Fig. 1 has been shown to be effective against many viral infections including Ebola. Referring particularly now to the experimental data shown in Table I, in concentration Ec50 the TZV molecule is potent and safe in in vitro assays and can reduce viral replication by 50%. The method of treatment of viral infections in mammals (Dengue, Ebola, West Nile, Flu) especially humans, would be to orally administer a compound containing the TZV molecule of Fig. 1 until the virus is reduced or eliminated.

Fig. l

TABLE 1