DE2529533A1 - 3-Deazaguanines - with antiviral, antitumour and antibacterial activity, and intermediates - Google Patents

Abstract

3-Deazaguianines of formulae Ib and inters. Ia are new together with their acid-addn. salts (where X is NH -NH2 or -OMe; Y is CNHR, CNR' or -CN; R is H or acyl; R' is =CH.NME; Z is H, tetrahydropyranyl beta-D-ribofuranosyl, 5-deoxy-beta-D-ribofuranosyl, beta-D-ribo-furanosyl-5-phosphate, cyclic beta-D-ribofuranosyl-3,5-phosphate, 1-18C acyl and isopropylidene, 1-18C acyl and isopropylidene-5-deoxy-beta-D-ribofuranosyl, 1-18C acyl and isopropylidene-beta-D-ribofuranosyl-5-phosphate or 1-18C acyl-beta-D-ribofurnosyl-3,5-cyclic phosphate; provided that X is NH and Y is C.NHR or CNR and only if X and Y are bound, and X is NH2 or -OMe and Y is -CN only if X and Y are not bound). Cpds. of formulae (where Z is beta-D-ribofuranosyl-5-phosphate, 5-deoxy-beta-D-ribo-furanosyl, ribofuranosyl-3,5-cyclic phosphate, H, tetrahydropyranyl or beta-D-ribofuranosyl) are specif. claimed.

Description

3-deazaguanine as well as derivatives of this compound During the last Ten years it has been found that many nucleoside analogs are good anti-tumor as well as possessing antivirus activities. From the previously known synthetic nucleosidic Antiviral and anti-tumor agents are 5-iodine-2'-deoxuridine (IDU), 9-ß-D-arabinofurano syladenine (Ara-A) and 1-ß-D-arabinofuranosylcytosine (Ara-C) are the most important.

viewed. However, these compounds are only effective as antiviral agents effective against a limited spectrum of viruses, this spectrum not being those Includes viruses that cause diseases of the respiratory system in humans (flu and common cold). The only nucleoside analog known of which is that it is against these viruses that cause respiratory disease active is 1-ß-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, which is described in US Pat 3 798 209 is described.

Certain derivatives of this last-mentioned compound also have as found, significant antiviral activity, in fact such as the triazole bases 1,2,4-triazole-3-carboxamide and 1,2,4-triazole-3-thiocarboxamide. Despite the existence of these compounds and despite the discovery of their antiviral activity There is still a need for compounds that are effective in infecting viruses able to inhibit, in particular infections of the respiratory organs caused by viruses as a result.

The known nucleosidic anti-tumor agents have the disadvantage afflicted that they are either toxic to the transducer or not broad Have spectrum of their antitumor activity.

If nucleoside analogs are used, either a virus or To inhibit tumor growth, the nucleosides are then converted into their corresponding in vivo Mono- or polyphosphates, which are the actual inhibitors of such Growth are metalized. The main obstacle to the use of nucleoside analogs In the way of chemotherapy, however, is the appearance of a resilience of the cells compared to such compounds, since the attacking cells have a low Exhibit degree of kinase or pyrophosphorylase activity and consequently none produce effective inhibitors. Even if this problem is caused by a use of If nucleoside phosphates can be dissolved, such derivatives often have the disadvantage indicate that they do not pass through the cell membrane or quickly in the intercellular fluid are decomposed so that they become ineffective as inhibitors.

In view of the above considerations, it can be seen that There is a need for analogs which are effective in the development of viral infections as well as being able to inhibit or inhibit neoplasms, and which is also a better one Possess solubility as heretofore known antiviral and antitumor agents. The provision such a connection that not just a decent activity but is also able to penetrate the cell membrane and However, contacting the viral infection in effective concentrations is extreme difficult.

The invention relates to compounds of the structure and a process for their preparation, in which X is NH, -NH2 or -OCH3, Y> CNHR, CNR1 or -CN, where RH is or acyl and R1 = CH-N (CH3) 2 symbolizes, while Z is H, Tetrahydropyranyl, ß-D-ribofuranosyl, 5-deoxy-ß-D-rihofuranosyl, ß-D-ribofuranosyl-5-phosphate, ß-D-ribofuranoxyl-3,5-cyclisechs PhosPhat, C1-C18-acyl and isopropylidene-ß -D-ribofuranosyl, C1-C18-acyl and isopropylidene-ß-D-ribofuranosyl, C1 -C18-acyl and isopropylidene-5-deoxy-ß-D-ribofuranosyl, C1-C18-Ocyl and isopropylidene-ß-D-ribofuranosyl -5-phosphate or C1-C18-acyl-ß-D-ribofuranosyl-3,5-cyclic phosphate. The physiologically acceptable salts of these compounds also fall within the scope of the invention, provided that X only stands for> NH and Y for> CNHR or> CNR1 if X and Y are connected to one another, and X only then --NH2 or - OCH3 and Y is -CrN when X and Y are not linked to one another.

The compounds according to the invention are suitable as antiviral agents, Anti-tumor agents as well as antibacterial agents.

The compounds of the present invention can be made according to the following Reaction scheme are prepared, examples illustrating their preparation. The temperatures and melting points are given in "C. The melting points are determined using a Thomas Ioover capillary melting point apparatus and are not corrected. Specific rotations are made in a 1 dm tube below Use of an automatically operating digital polarimeter (Perkin-Elmer model 141) measured. The proton magnetic resonance (PMR) spectra are obtained using a Varian A-60 spectrometer and a Hitachi R-20A spectrometer measured in DMSo-d6, using DSS as the reference standard. The UV spectra are used a spectrophotometer (Cary model 15) as well as the infrared spectra using on a spectrophotometer (Perkin-Elmer 257) (KBr pellets). The elemental analyzes were performed by Galbraith Laboratories, Inc., Knoxville, Tenn. the Evaporation occurs under reduced pressure with a bath temperature below 400C executed. The components are identified on silica gel (ICN, Woelm F254) by UV light and by spraying with a 10% solution of sulfuric acid in methanol and subsequent heating.

Compatible acid addition salts of the basic portion can, for example from the hydrochloride, hydrobromide, hydroiodide, citrate, sulfate, a substituted one Sulphate, phosphate, carbonate, bicarbonate or formate are made, this listing however, it is not intended to imply any limitation. Compatible salts of the phosphate component can consist of the alkali and alkaline earth salts, for example of sodium, Potassium, calcium, magnesium, lithium, ammonium and substituted ammonium, Trialkylammonium, dialkylammonium, alkylammonium, for example triethylammonium, Trimethylammonium, diethylammonium, octylammonium, cetyltrimethylammonium or Cetylpyridium salts, although this list is also not a restriction target.

The hydroxyl groups on the glycone as well as the amino group of the heterocycle can be blocked with groups, for example with an acyl group, isopropylidene group or dimethylaminomethylene group, although this list is not a limitation target. The acyl group can be selected from a group consisting of a straight chain, branched, substituted, unsaturated, saturated or aromatic acid consists, for example, acetic acid, trifluoroacetic acid, propionic acid, n-butyric acid, Isobutyric acid, valeric acid, caproic acid, pelargonic acid, enanthic acid, caprylic acid, Lactic acid, acrylic acid, propargylic acid, palmitic acid, benzoic acid, phthalic acid, Salicylic acid, cinnamic acid or naphthoic acid, this enumeration also only is exemplary.

Scheme I. Scheme I (continued) Scheme II As can be seen from the schemes, the compounds can be prepared from methyl 4 (5) acetamide-2-imidazole-5 (4) carboxylate (compound 2), which is treated with a dehydrating agent such as phosphorus oxychloride, oxalyl chloride, thionyl chloride etc., is reacted under reflux conditions, whereby Met: hyl-4 (5) -cyanomethyl-2-imidazole-5 (4) -carboxylate (compound 3) is obtained, which then with liquid ammonia at a temperature between about 100 and 1500C to obtain 4 (5) -cyanomethyl-4-imidazole-5 (4) -carboxamide (compound 4) is heated (cf. Examples 1 to 3).

This connection (3 is then refluxed with a Alkali metal carbonate, such as sodium carbonate, to produce 3-deazaguanine (compound 5) implemented. Optionally, 3-deazaguanine can be obtained directly from the cyanomethyl carboxylate by treatment with ammonium chloride in an aliphatic alcohol such as methanol etc., in the presence of ammonia at a temperature between about 100 and about 1500C can be produced (see Example 4).

The connections 9, 10, 11, 12, 13 and 14 can be derived from the connection 3, using a high temperature melting process with a proprietary Ribofuranose or a conversion to its silylated derivative and a conversion with a protected ribofuranose in the presence of tin (IV) chloride and a subsequent one Amination and ring closure can be carried out. Optionally, the connections 11 and 14 can be produced from 3-deazaguanine by direct glycosidation (cf. Examples 5 to 7).

The tetrahydropyranyl derivatives (compounds 15 to 20) and the 5'-deoxyribofuranosyl derivatives (Compounds 21 to 26) can also be prepared in a similar manner (cf. Examples 8 and 9 and Reaction Scheme I).

The 5'-phosphates can be phosphorylated by two different Precursors are produced (see. Scheme II). Example 10 shows the phosphorylation of 5 (4) -cyanomethyl-1-ß-D-ribofuranosylimidazole-4 (5) -carboxamide and the example 11 phosphorylation of compounds 11 and 14. The 3 ', 5'-cyclic Phosphates (compounds 28 and 31) are (see. Example 12) from the compounds 27 or 29 established, while the connection 31 is established via the connection 28 as shown in Scheme II.

The compounds according to the invention can also be blocked, as can be seen from Scheme II. Example 13 shows a blockage on the Sugar content (compounds 32 and 33), the blocking can also be on the aglycon (Compound 34) or on both the sugar and the aglycone (Compound 35).

3-deazaguanosine (compound 11) can also be obtained by enzymatic conversion from 3-deazaguanine, as can be seen from Example 14.

Example 1 Methyl 4 (5) acetamido-2-imidazole-5 (4) carboxylate (compound 2) Dimethyl 4-acetic acid-2-imidazole-5-carboxylate (compound 1, cf. R.K. Robins et al, J. Org. Chem., 28, 3041 (1963) is used in an amount of 20.4 g (0.013 Mol) to 1800 ml of methanol, which has been saturated with ammonia at OOC, added, whereupon the resulting amber solution over a period of 16 hours is stirred at room temperature. The light orange colored solution is in vacuo evaporated to dryness. The residue is triturated with 50 ml of methanol, then collected and air dried. This gives compound 2 in one Amount of 16.6 g (88%). F. 230 to 2320C (literature melting point 242 to 2440C).

Example 2 Methyl 4 (5) -cyanomethylimidazole-5 (4) -carboxylate (Compound 3) 16.6 g (0.097 mol) of compound 2 are in 800 ml of phosphorus oxychloride during refluxed for a period of 3 hours. The excess phosphorus oxychloride is removed in vacuo, whereupon the residue is hydrolyzed with 100 ml of ice water at OOC will. The solution is neutralized to a pH of 6 below 150C. To The precipitate is filtered off, washed and dried for 16 hours. You get Compound 3 in the amount of 12.4 g (77); F. 168 to 1700C. An analysis sample melts at 170 to 171 ° C. #maxpH 1 222 nm, 10 700 # maxpH11 251 nm, 10 600 NMR (DMSO-d6) # 3.89 (s, 3H, CH3), # 4.20 (s, 2H, CH2), 7.90 (s, 1H, H2), 13.3 (Br, 1H, NIt analysis: Calculated for C7H7O2N3: C 50.91, H 4.27, N 25.45 Found: C 50.70, H 4.25, N25.35 Example 3 4 (5) -Cyanomethylimidazole-5 (4) -carboxamide (compound 4) 5.0 g (0.03 mol) of the compound 3 with 200 ml of a liquid ammonia during heated for a period of 48 hours.

The excess ammonia is evaporated, whereupon the residue in approx. 20 ml of water is taken up, filtered and air-dried. Receives 2.85 g (62.5 t) of compound 4 (m.p. 225 to 2280C). An analysis sample melts at 230 to 232 ° C.

Analysis: Calculated for C6H6N4O: C 48.00, H 4.03, N 37.32 Found: C 48.14, H 3.97, N 37.51 Example 4 6-Aminoimidazo [4,5-c3-pyridin-4-one (3-Deaazaguanine) (Compound 5) Method A.: 1.5 g (0.01 mol) of Compound 4 are used in 15 ml of a 10% Na2CO3 solution for a period of 4 hours am Maintained reflux to pH 6 with concentrated hydrochloric acid neutralized and then left to stand at 4 "C for a period of 16 hours. The solid obtained is collected, washed and dried. You get 750 mg (50%) of compound 4. F. 3000C.

Analysis: Calculated for C6H6ON4 :. C 48.00, H 4.03, N 37.32 Found: C 47.99, H 4.10, N 37.19 Method B .: 5.0 g (0.0303 mol) of compound 3 become in 200 ml of liquid ammonia at 1000C for a period of 96 hours heated. The ammonia is evaporated and the residue is dissolved in 60 ml of H2, is collected and dried.

This gives 2.85 g (56 t) of the product with a F. of 3000C. The physical constants are the same as in the case of according to the method A obtained product.

Method C: A solution of 0.50 g (3 mmol) of compound 3 and 0.50 g of NH4Cl in 20 ml of methanol, into the NH3 over a period of 2 minutes Room temperature, is sealed and placed in an oil bath at heated to a temperature of 1500C for a period of 16 hours. Of the The contents are evaporated, taken up in 20 ml of hot water and filtered. the Thin-layer chromatography gives 3-deazaguanine as the only detectable product in 33% yield.

Example 5 Methyl-5-cyanomethyl-1- (β-D-2 ', 3', 5'-tri-O-acetyl- or -benzoylribofuranosyl) -imidazole-4-carboxylate (compound 9) and methyl-4-cyanomethyl-1-B-D-2 ', 3', 5'-tri-o-acetyl- or -benzoylribofuranosyl) imidazole-5-carboxylate (Compound 12) Method A .: 1.86 g (11 mmol) of methyl-4 (5) -cyanomethylimidazole-4 (5) -carboxylate (compound 3) are thoroughly mixed with 1,2,3,5-O-tetraacetylribose (compound 7a) in an amount of 4.77 g (15 mmol). The mixture is in an oil bath melted together at 1700C for a period of 7 to 8 minutes. 200 mg of chloroacetic acid are added, whereupon a vacuum is applied, with the Temperature is increased rapidly to 1900C. The entire period after the addition of the catalyst is 25 minutes.

The product is extracted with benzene, filtered and saturated with a Na2Co3 solution and then washed with H20. The benzene is dried and filtered and is evaporated. The gum obtained as a residue is on a silica column chromatographed using CHCl3 with increasing concentrations of MeOH. The fractions containing the product are poured together and evaporated will. Then crystallization from MeOH takes place. This is how you get the connection 12a in an amount of 1.7 g. # Max pH7 & 11 242 mµ, F. 92-93 ° C, PMR (in CDCL3) # 6.45 (1.3, H1, JH1'-H2 '= 2.5 Hz).

Analysis: Calculated for C18H21N3O9 C 51.06, H 5.00, N 9.93 Found: C 51.23, H 5.03, N 9.90.

The other isomer (Compound 9a) becomes in a yield of less insulated than 10 t.

The same. Melt method is using 2,3,5-tri-O-benzoyl -1-O-acetyl ribofuranose (Compound 7b) applied. A mixture of two is also possible Isomers (Compounds 9b and 12b) as determined by the PMR spectrum in an overall yield received by 47%.

Method B .: 1.65 g (10 ml Period of 18 hours with 25 ml of hexamethyldisilazane and 50 mg (NH4) 2SO4 at reflux held. The excess of hexamethyldisilazane is removed. The product (compound 6) is dissolved in 200 ml of dichloroethane. 3.18 g (10 mmol) of tetraacetyl ribose (Compound 7a) are added, followed by the addition of 0.08 ml SnCl4. the The reaction mixture is left at room temperature for a period of 6 hours touched.

A saturated Na2CO3 solution is then added. It will be during stirred for half an hour. The organic phase is mixed with a Na2CO3 solution and washed with water, dried, filtered and evaporated. The as residue accruing gum is cleaned according to method A. This gives you the connections 9a and 12a in 5% yield. The ratio of compound 9a to compound 12a is 2: 1 as determined by UV absorption.

This procedure uses 2,3,5-tri-O-benzoyl-1-O-acetylribofuranose (Compound 7h) is repeated, then an isomeric mixture of products 9b is obtained and 12b in more than 60% yield in the form of a white foam. The relationship the connection 9b to the connection 12b is 5: 1.

Method C .: 10 mmol of compound 6 are dissolved in 100 ml of CH3CN. 2,3,5-Tri-O-acetylribofuranosyl bromide is dissolved in an amount of 10 mmol in 25 ml of CH3CN, added. The mixture is kept at room temperature for a Stirred for a period of 3 days. Then 10 ml of MeOH are added. The mix will then evaporated under vacuum. The gum obtained is after the Method A purified, with compounds 9a and 12a (in a ratio of 1: 8).

The procedure is performed using 2,3,5-tri-O-benzoylribofuranosyl bromide (Compound 8b) repeated, the compounds 9b and 12b being obtained as products will.

Method D :: 25.0 g of compound 3 are taken under anhydrous conditions over a period of 12 hours with 300 ml. hexamethyldisilazane and 0.5 g Treated ammonium sulfate at reflux.

The excess of hexamethyldisilazane is removed by distillation. The oil remaining as a residue is dissolved in 800 ml of a dry 1,2-dichloroethane dissolved, whereupon 76.5 g of 1-O-acetyl-2,3,5-tri-O-benzoyl-ß-D-ribofuranose and 25.4 g of tin (IV) chloride are added to the solution. Thin layer chromatography shows practically complete conversion to the nucleoside after 15 minutes. The reaction mixture is further stirred for a period of 4 to 24 hours and then in 3 1 of a 5% sodium hydrogen carbonate solution poured in. The mixture is through Celite filtered, extracted with 3 x 800 ml of chloroform, whereupon the extracts combined will. The extracts are dried with MgSO4 and under reduced pressure (500C) evaporated. 92 g (100%) of a light beige foam are obtained from the compound 9b. An analytical sample is obtained in such a way that 1 g of the foam is dissolved in benzene / ethyl acetate (1: 1), is passed through a silica gel column (10 g>. A white foam is obtained. PMR (DMSO-dJ; & 3.85 (s, 3, CH3) 4.52 (s, 2, CH2), 6.6 (d, 1, J = 5 Hz, H ,,), 8.38 (s, 1, C2H).

Analysis: Calculated for C33H27N3N3Og: C 65.02, H 4.46, N 6.89 Found: C 65.19, H 4.46, N 6.63 Method E .: 1.65 g (10 mmol) methyl-5 (4) -cyanomethylimidazole-4 (5) -carboxylate (compound 3) with 3.18 g (10 mmol) 1,2,3,5-Tetra-O-acetylribofuranose mixed and heated to 1700C until melting has taken place (approx. 1 minute). 20 mg bis (pnitrophenyl) phosphate are added, followed by heating at 170 to 1750C under a high vacuum continued for a period of 25 minutes. The residue is in Dissolved chloroform, extracted with a 5% NaHCO3 solution and dried with MgSO4. Then it is applied to a silica gel column (120 g, packed in CHCl3). The elution with AtOAc results in the following four pure nucleosides: methyl 4-cyanomethyl-1- (2,3,5-tri-O-acetyl-ß-D-ribOfuranosyl) -imidazole-5-carboxylate (compound 12a) in the form of white needles (2.0 g ,, 47%), m.p. 92 to 93 ° C (EtOH), # maxpH7 & 11 242 mµ, PMR (DMSO-d6) g2.13 (s, 9, acetyl CH3 's), 3.87 (s, 3, ester CH3), 4.19 (s, 2, CH2), 6.48 (d, JH1'-H '= 3 Hz, H1,), 8.33 (s, 1, C2H).

Analysis: Calculated for C18H21N3Og: C 51.06, H 5.00, N 9.93 Found: C 51.23, H 5.03, N 9.90 methyl-4-cyanomethyl-1 - (2,3,5-tri-O-acetyl-ct-D-ribofuranosyl) -imidazole-5-carboxylate (compound 12c) in the form of a syrup (0.5 g, 11.8 8 pH1 238 mpt (& 9 800), hPaH7 & 11 247 (11 550), max max PMR (DMSO-d6): # 2.13 (s, 9, Acetyl CH3 's), 3.86 (s, 3, ester CH3), 4.19 (s, 2, CH2), 6.48 (d, JH1'-H2 = 5 Hz, 1, H1,), 8.18 (s, 1, C2H).

Analysis: Calculated for: C18H21 N3O9: C 51.06, H 5.00, N 9.93 Found: C 51.32, H 4.98, N 9.84 methyl 5-cyanomethyl-1- (2,3,5-tri-o -acetyl-β-D-ribofuranosyl) imidazole-4-carboxylate (Compound 9a) in the form of a syrup (0.8 g, 19%). This material is identical with the only isomer, that according to the tin (IV) chloride method has been made.

Methyl 5-cyanomethyl-1- (2,3,5-tri-o-acetyl-α-D-ribofuranosyl) -imidazole-4-carboxylate (Compound 9c) in the form of a syrup (0.2 g, 4.7% # maxpH1 226 (# 10 100), # maxpH7 236 (10 500), # maxpH11 238 (10 900), PMR (DMSO-d6), 1.93, 2.04 and 2.13 (singlets, 3 protons each, acetyl CH3 groups), 3.84 (s, 3, ester CH3), 4.35 (s, 2, CH2), 6.49 (d, 1, JH1'-H2 ', = 6 Hz, 1, H1'), 8.03 (s, 1, C211) Analysis: Calculated for C18H21N3O9: C 51.06, H 5.00, N 9.93 Found: C 51.28, H 4.78, N 9.71 Example 6 5-Cyanomethyl- 1-β-D-r ibofuranosylimidazole-4-carboxamide (Compound 10) 0.046 moles of the compound 9a or 9b and 150 ml of liquid ammonia are placed in a bomb at steam bath temperature heated for a period of 3 hours. The ammonia is at room temperature evaporated while the last traces of NH3 are removed in vacuo. The residue is on a silica gel column (25 g) by eluting with chloroform / methanol (4: 1) cleaned. The fractions containing compound 10 are pooled and evaporated until crystallization begins.

The yield of compound 10 is 10.5 g (81%). F. 90 to 91 ° C. [α] D25 - 46.9 ° C fc 1.04, water), TR cm 1 (KBr) 2250 (w) (C = N), 1666 (s) (C = 0), # maxpH1 217 nm (# 8 8 750), 231 (shoulder) (8 190), max pH7 219 max (shoulder) (8 190) 232 (8 760) # maxpH11 234 (8750), PMR (DMSO-d6): # 4.52 (s, 2, CH2), 5.71 (d, 1, J = 6 Hz, H1,), 7.33 and 7.52 (s, 1, NH), 8.12 (s, 1, C2H) Analysis: Calculated for C11H14N405: C 46.81, H 5.00, N 19.85 Found: C 46.61, H 5.28, N 19.49 Example 7 6-Amino-1- (ß-D-ribofuranosyl) -imidazo (4,5-c) -pyridin-4-one (compound 11) (3-deazaguanosine) and 6-amino-3- (ß-D-ribofuranosyl) -imidazole, 5-cf-pyridin-4-one (compound 14) Method A: 846 mg (2 mmol) of compound 12a are dissolved in 200 ml of an anhydrous MeOH dissolved. The solution is saturated with ammonia at 40C. The reaction mixture is kept at room temperature in a tightly closed flask for a period of time stirred for 2 days. It is then carefully evaporated under vacuum, with a joint evaporation with AtOH / MeOH is carried out to remove the last traces of ammonia to remove. The residue is extracted with 4 x 20 ml CHCl3. The solid will recrystallized from H2 0. This gives 310 mg (55%) of the compound 14. F. 247 to 250c, # maxpH1 278 and 320, max 259 and 325 and # maxpH1 322.

Analysis: Calculated for C11 H14N4O5 C 46.81, H 5.00, N 19.85 Found: C 47.03, H 4.06, N 19.84 An identical product is found in 52% yield obtained when compound 12b is exposed to similar reaction conditions. The product 14 is also made by heating either the compound 12a or 12b in liquid ammonia at 110 to 120 ° C for a period of 10 to 12 hours preserved in a steel bomb.

Similarly, the connections 9a or 9b are made into the connection 11 in 45 to 50% yield using either MeOH / ammonia at room temperature or liquid ammonia at 110 converted to 1200C. The product is isolated by thin layer chromatography (cellulose F plates, developed in CH3CN: H20, 7/3, V / V) and has a UV absorption # maxpH1 of 284 and 314 (shoulder), # maxpH1 270 and 305 (shoulder), # maxpH11 268 and 296 (shoulder), F. 2640C.

Analysis: Calculated for C11H14N405: C 46.81, H 5.00, N 19.85 Found: C 46.68, H 5.12, N 19.61 Method B .: 150 mg (1 mmol) 6-aminoimidazo4,5-c-pyridin-4-one t (3-deazaguanine, compound 5) a are refluxed in the presence of 10 ml of hexamethyldisilazane and heated approximately 10 mg NH4) 2SO4 over a period of 18 hours. Of the Excess of hexamethyldisila.zan is removed in vacuo, whereupon the residue is taken up in 50 ml of CH3CN. 340 mg (1 mmol) of compound 8, also dissolved in 10 ml of CH3CN, are added, followed by the reaction mixture for a period of time is stirred for 3 days under anhydrous conditions at room temperature.

Then 5 ml of MeOH are added. The reaction mixture is during stirred for a further 10 minutes. It is then evaporated and redissolved in MeOH which has been saturated with ammonia and at room temperature left overnight. Thin layer chromatography gives a number of UV-absorbing products, two of these products being the compound 11 and 14 correspond. The UV absorption spectra of these two products are identical to those of compounds 11 and 14.

Method C .: A mixture of 4.64 g (20 mmol) of compound 10, 50 ml of a 5% sodium carbonate solution and 25 ml of ethanol are added while stirring refluxed for a period of 0.5 hours. The solution is filtered, cooled and allowed to crystallize. The crystals are filtered, washed and dried. This gives 4.0 g of needles. Another 0.8 g off of the mother liquor give a yield of 4.8 g (85%). F. 255 to 257 ° C (decomposition). [α] 25 D - 59.3 (C 0.97). 1n NaOH, UV # maxpH1 284 nm (# 13 650), 309 (shoulder) (6 570), # maxpH7 270 (10 120), 298 (8 140), # maxpH11 272 (10 120), 295 (shoulder) (8 140), PMR (DMSO-d6): # 5.51 (d, 1, J = 6 Hz, H1,), 5.52 (s, 1, C7H), 5.68 (s, 2, NH2), 7.95 (s, 1, C2H), 10.5 (s, 1, NH).

Example 8 Methyl 4-cyanomethyl-1- (tetrahydropyran-2-yl) -imidazole-5-carboxylate (Compound 18) and methyl 5-cyanomethyl-1- (tetrahydropyran-2-yl) -imidazole-4-carboxylate (Compound 15) A mixture of 12.4 g (75.2 mmol) of methyl 4- (5) -cyanomethylimidazole-5 (4) -carboxylate, 15 ml of a freshly distilled dihydropyran, 75 mg bis (p-nitrophenyl) phosphate and 250 ml of dry ethyl acetate is added over a period of 10 hours held at reflux. Another 10 ml dihydropyran and 25 mg bis (p-nitrophenyl) phosphate are added, then the reflux treatment over a period of 5 hours is continued. The solution is evaporated in vacuo to a syrup, which by Chromatography on a silica gel column (500 g) is purified. The elution takes place with chloroform / ethyl acetate (1: 1). This gives 11.1 g (59%) of methyl 4-cyanomethyl-1- (tetrahydropyran-2-yl) -imidazole-5-carboxylate. Recrystallization from ligroin / ether (30 to 60 ° C) results in white rosettes. F. 82 to 830C, IR cm 1 (KBr): 1720 (s) (C = O), 2260 (m) (C = N), WhPH1 222 nm (# 11 020), 2 PH5 242 nm (# 12 100), max max hmajl 242 nm (612 100), PMR (DMSO-d6): # 3.88 (s, 3, CH3), 4.14 (s, 2, CH2), 5.90. (m, 1, H2,), 8.22 (s, 1, C2H).

Analysis: Calculated for C12H15N303: C 57.82, H 6.07, N 16.86 Found: C 57.78, H 6.26, N 16.70 Another elution with chloroform / acetone (1: 1) gives 6.2 g (33%) of methyl 5-cyanomethyl-1- (tetrahydropyran-2-yl) imidazole-4-carboxylate. Recrystallization from ligroin / ether (30 to 600C) results in white needles. F. 98 to 99 ° C, IR cm (KBr): 1718 (s) (C = O), 2240 (W) (C = N), # maxpH1 220 nm (# 11 080), # maxpH7 240 nm (# 10 050), # maxpH11 242 nm (# 9 820); PMR (DMSO-d6): # 3.85 (s, 3, CI-I3), 4.40 (s, 2, CH2) 5.51 (mt1, H2,), 8.08 (s, 1, C2H).

Analysis: Calculated for C12H15N3O3: C 57.82 H 6.07, N 16.86 Found: C 57.98, H 6.21, N 17.07 5-cyanomethyl-1- (tetrahydropyran-2-yl) -imidazole-4-carboxamide (Compound 16) 0.60 g (2.41 mmol) of methyl 5-cyanomethyl-1- (tetrahydropyran-2-yl) -imidazole-4-carboxylate and 10 ml of liquid ammonia are in a steel bomb with a capacity of 40 ml filled.

The bomb is three-quarters immersed in a steam room and during heated over a period of 3 hours. At this point, thin layer chromatography reveals (Chloroform / methanol, 9: 1, silica gel) complete conversion of the starting material into the carboxamide and a trace of 3-deaza-9- (tetrahydropyran-2-yl) guanine.

The ammonia is allowed to evaporate at room temperature. The residue is placed under vacuum overnight to remove the last traces of ammonia. The greenish-brown residue is recrystallized from methanol (activated charcoal). Included 0.4 g of C71%) of the desired compound is obtained in the form of light yellow needles.

F, 198 to 199 ° C after drying at 100 ° C for a period of time of 3 hours. IR cm-1 (KBr): 1685 (s) (C = O), 2250 (W) (C = N), 3140 (s) and 3300 (s) NH2, PMR (DMSO-d6): # 4.50 (s, 1, CH2), 5.45 (m, 1, H2,), 7.35 (s, 1, NH), 7.53 (s, 1, NH), 8.03 (s, 1, C2H).

Analysis: Calculated for C11H14NdO2: C 56.39, H 6.02, N 23.91 Found: C 56.59, H 6.28, N 23.91 6-Amino-1- (tetrahydropyran-2-yl) imidazo [4,5- c] pyridine-4 (5H) -one (compound 17) A mixture of 702 mg (3 mmol) 5-cyanomethyl-1- (tetrahydropyran-2-yl) -imidazole-4-carboxamide, 6 ml of a 5 8igcn aqueous sodium carbonate solution and 10 ml of ethanol is used during refluxed for a period of 20 minutes. After the reflux starts, complete dissolution is determined.

The product precipitates on further reflux treatment. The suspension is cooled and filtered. The residue is washed thoroughly with water and then with Ethanol (690 mg, 97%).

Recrystallization from a large volume of ethanol / water (1: 1) yields white needles (F. 268 to 2690C, decomposition) after drying at 100 ° C for a period of 5 hours.

H1 285 #max 203 (# 13 400), 313 nm (shoulder) (# @ @@@), max 270 nm (C12 600), 300 nm (# 9 350), PaH11 272 nm (# 12 400 !, 295 nm (# 9 130), PMR (DMSO-d6-NaOD): # 5.22 (m, 1, H2,), 5.58 (s, 1, C6H), 7.68 (s, 1, C2H).

Analysis: Calculated for C11H14N402: C 56.39, H 6.02, N 23.91 Found: C 56.51, II 6.15, N 23.93 6-Amino-3- (tetrahydropyran-2-yl) -imidazo [4,5- c] -pyridin-4 (5H) -one (Compound 20) A mixture of 2.49 g (10 mmol) of methyl 4-cyanomethyl-1- (tetrahydropyran-2-yl) imidazole-5-carboxylate and 20 ml of a liquid ammonia is put into a steel bomb with a capacity from 40 ml and heated to 100 ° C (oil bath) over a period of 5 hours. The ammonia is allowed to evaporate at room temperature. The residue is over Vacuum exposure at night. Recrystallization from methanol (Activated charcoal) provides the desired compound in an amount of 1.1 g (47%) in Form of whitish needles. F. 2080C (decomposition) after drying at 1000C for a period of 2 hours. UV # max pH1 275 nm (# 12 300), 317 nm (6 6 140), X PH7 257 nm (6. 800), 315 nm (67 68O), # max pH11 257 nm (& 6 580), max 315 nm (& 7 450), PMR (DMSO-d6): 5.38 {s, 2, NH2), 5.58 (s, 1, C7H), 6.05 (m, 1, H2,), 8.22 (s, 1, C2H), 10.62 (s, 1, NH).

Analysis: Calculated for C11H14N402: C 56.39, H 6.02, N 23.91 Found: C 56.21, H 5.96, N 23.77 Example 9 methyl-5-cyanomethyl-1- (5-deoxy-2,3-di-o-acetyl-β-D-ribofuranosyl) imidazole-4- carboxylate (Compound 21) 2.22 g (13.4 mmol) of methyl 5 (4) -cyanomethylimidazole-4-carboxylate are used under anhydrous conditions for a period of 12 hours Treated 25 ml of hexamethyldisilazane and 50 mg of ammonium sulfate under reflux. The excess of hexamethyldisilazane is removed by distillation under reduced pressure, the trimethylsilyl derivative being obtained in the form of a yellowish-brown oil. This is dissolved in 35 ml of 1,2-dichloroethane.

3.4 g (13.4 mmol) of 5-deoxy-1,2,3-tri-o-acetyl-ß-D-ribofuranose become added to the solution, followed by an addition of 2.25 ml (19.3 mmol) of tin (IV) chloride connects. The solution is at room temperature for a period of 9 Stirred for hours.

100 ml of a 7% sodium hydrogen carbonate solution are added, on what Is extracted 2 x with chloroform. The dried organic layer is in vacuo evaporated. The residue is dissolved in chloroform and placed on a silica gel column (200 g, packed in chloroform). Elution with ethyl acetate yields 2.2 g (45%) of the nucleosidide in the form of a colorless syrup.

UV # max pH1 225 nm (# 1O 25O), # max pH7 235 nm (1O 750), # max pH11 238 nm 610 250), PMR (DMSO-d6): γ 1.45 (d, 3, CH3) 2.08, 2.13 (s, 3, COCH3) 3.85 (s, 3, CO2CH3), 4.45 (s, 2, CH2), 6.05 (d, 1, H1 '), J = 5Hz, 8.25 (s, 1, C2H) Analysis: Calculated for C16H1gN307 C 52.60, II 5.24, N 11.50 Found: C 52.40, H 5.31, N 11.26 5-cyanomethyl-1- (5-deoxy-β-D-ribofuranosyl) - imidazole-4-carboxamide (Compound 22) A mixture of 2.20 g (6.03 mmol) of methyl-5-cyanomethyl-1- (5-decoxy-2,3-di-o-acetyl-β-D-ribofuranosyl) -imidazole-4 carboxylate and 30 ml of liquid ammonia is placed in a steel bomb with a capacity of 40 ml and heated to 100 ° C over a period of 7 hours. That Ammonia is allowed to evaporate. The residue is left overnight for removal the last traces exposed to the action of a vacuum. The residue is on 5 g of silica gel absorbed and placed on a silica gel column (60 g, packed in chloroform) given up. Elution with chloroform / methanol (4: 1) gives the pure product. Recrystallization from methanol gives 1.42 colorless cubes g (88%).

Mp 173-174 ° C after drying at 1000C for a period of time of 3 hours. [α] 25-47.8 (C = 1, H2O), UV mPHa1 218 nm (# 1O OOO), # max pH7 233 nm (# 1O 2OO), # max pH11 234 nm (# 9 730), PMR (DMSO-d6): a 1.35 (d, 3, CH), 5.66 (d, 1, H1 '), J = 5Hz, 7.45 (d, 2, NH2), 8.02 (s, 1, C2H).

Analysis: Calculated for C11H14N4O4: C 49.62 H 5.30 N 21.04 Found: C 49.44 H 5.20, N 20.92 6-Amino-1- (5-deoxy-β-D-ribofuranosyl) -imidazo [4,5-c] -pyridine-4 (5H) on (compound 23) Mine mixture of 1.1 1 (4.13 (4, 1 3 mmol) 5-cyanomethyl- 1 (5-deoxy-ß-D-ribofuranosyl) -imidazole-4-carboxamide, 7 ml of a 5% aqueous sodium carbonate solution and 6 ml of ethanol are refluxed stirred for 0.75 hours, treated with activated charcoal and filtered through celite. The light yellow, speckled crystals are filtered, washed with water and then with ethanol. Drying takes place at 1000C during a period of 5 hours and yields 0.9 g (82%) of the product. F.> 310 ° C, [@] D25 - 65.6 (C = 1, 0.1 n NaOH), UV # maxpH1 294 nm (# 13,000), 308 nm (shoulder) (# 6 920), #maxpH 272 nm (# 12 200), 299 nm (# 9 150), (pH11 272 nm (# 12 200) 285 nm (shoulder) (# 9 150) BMF (DMSO-d).

max # 1.36 (d, 3, CH3), J = 6Hz, 5.52 (s, 1, C7H) 5.55 (d, 1, H1,), J = 5 Hz, 5.75 (2, NH2), 7.90 (s, 1, C2H).

Analysis: Calculated for C11H14N404: C 49.62, H 5.30, N 21.04 Found: C 49.66, H 5.37, N 21.20 methyl 4-cyanomethyl 1- (2,3-di-O-acetyl-5-deoxy-β-D-ribofuranosyl) imidazole-5-carboxylate (Compound 24) and methyl 5-cyanomethyl-1- (2,3-di-0-acetyl-5-deoxy-β-D-ribofuranosyl) -imidazole-4-carboxylate (Compound 21) 3.0 g (18.2 mmol) of methyl 5 (4) cyanomethylimidazole-4 (5) carboxylate are used under anhydrous conditions for a period of 12 hours Treated 50 ml of hexamethyldisilazane and 25 mg of ammonium sulfate on reflux. The excess of hexamethyldisilazane by distillation under reduced Pressure removed, leaving the trimethylsilyl derivative in the form of a yellowish-brown oil is obtained. The Cil is dissolved in 100 ml of a dry 1,2-dichloroethane. 4.73 g (18.2 mmol) of 5-dosoxy-1,2,3-tri-O-acetyl-D-ribofuranose is added to the solution, followed by the addition of 1.06 ml (9.1 mmol) of tin (TV) chloride in one portion connects.

The reaction solution is left at room temperature for a period of time stirred for 48 hours and then in 200 ml of a 7% sodium hydrogen carbonate solution poured. The mixture is filtered through Celite, extracted with 3 x 50 ml of chloroform, whereupon the combined extracts are dried with MgSO4 and under reduced pressure are evaporated at 500C to 6.6 g of a colorless oil.

Column chromatography (250 g silica gel, packed in chloroform, Elution with ethyl acetate) provides the first isomer that emerges from the column, Methyl 4-cyanomethyl 1- (2,3-di-oacetyl-5-deoxy-β-D-ribofuranosyl) -imidazole-5-carboxylate in an amount of 3.2 g (48 t). Recrystallization from ethanol gives colorless Needles. M.p. 123-124 ° C after drying at 650C for a period of time of 5 hours. UV # max pH1 234 nm (# 8 43O), # max pH7 & 11 242 nm (11 OOO), PMR, (DMSO-d6): 1.45 (d, 3, C5, CH3) J = 6Hz, 2.12, 2.15, (s, 3, COCH3), 3.85 (s, 3, CO2CH3), 4.2 (s, 2 , CH2), 6.39 (d, 1, H1 ') J = 3Hz, 8.34 (s, 1, C2H).

Analysis: Calculated for C16H19N307: C 52.60, H 5.24, N 11.50 Found: C 52.32, H 5.37, N 11.29. Further elution of the column with ethyl acetate gives Methyl 5-cyanomethyl-1- (2,3-di-o-acetyl-5-deoxy-β-D-ribofuranosyl) -imidazole-4-carboxylate in an amount of 1.7 g (26%). This material is the same as that prepared above Identical material (example 3).

6-Amino-3- (5-deoxy-β-D-ribofuranosyl) -imidazolo [4,5-c] -pyridine 4 (5H) -one (Compound 26) A mixture of 2.6 g (7.13 mmol) of methyl-4-cyanomethyl-1- (2,3-di-O-acetyl-5-deoxy-β-D-ribofuranosyl ) -imidazole-5-carboxylate and 25 ml of a liquid ammonia is in a SLah] bomb with a capacity of 40 ml for a period of 2.5 hours Heated to 1000C. The ammonia is allowed to evaporate at room temperature. The last Traces are removed by applying a high vacuum overnight. The greenish-brown one The residue is recrystallized from water (activated charcoal). This gives 1.3 g (68 t) of the nucleoside in the form of light yellow microcrystals.

P.

(# 11 700), 317 nm (# 5 98O), # max pH7 258 nm (# 6 500), 317 nm (# 7 53O), # max pH11 258 nm (# 6 500), 317 nm (# 7 28O), PMR (DMSO-d6): γ 1.35 (d, 3, C5, CH3) J = 6Hz), 5.38 (s, 2, NH2), 5.5 (s, 1, C7H), 6.24 (d, 1, H1r) J = 4Hz, 10.62 (brs, 1, NH).

Analysis: Calculated for C11H14N404: C 49.62, H 5.30, N 21.04 Found: C 49.42, H 5.28, N 20.86.

Example 10 5-Cyanomethyl-1-β-D-ribofuranosylimidazo-4-carboxamide-5'-phosphate (Compound 27) To a solution of 4.9 g (32 mmol) of phosphoryl chloride and 40 ml Trimethyl phosphate (be cooled to OOC using an ice bath under 2.26 g (8 mmol) of the powdered Compound 22 were added with stirring. The suspension is kept at 0 ° C (protected from moisture) for a period of 4 hours touched. A -complete dissolution will occur within 0.5 hours achieved. A Düiln layer chromatography (Al iquot hydrolyzed with water, silica gel, Acetonitrile-0.2m ammonium chloride, 3: 1) shows that a complete and flawless Conversion of the nucleoside into the nucleotide has taken place. The light beige solution will transferred dropwise to a flask in which 500 ml of an anhydrous ether be stirred vigorously. The ether is decanted off, whereupon another 250 ml of ether can be added to the returnable syrup. After stirring for a The ether is decanted for a period of 10 minutes. This procedure is still going to repeated once with another 250 ml of ether.

The remaining syrup is dissolved in 50 y of crushed ice, whereupon the solution is extracted with 2 x 50 ml of chloroform. The aqueous solution is then left to stand overnight at room temperature and adjusted to pH adjusted from 8 using a 1N sodium hydroxide solution. She will then applied to a column filled with Bio-Rad AG-1x8 (formate form, 50-100 mesh, 50 ml). The column is first filled with 250 ml of water and then with a gradient Von 0.2m to 0.5m formic acid (1 l each) washed. The product appears after approx. 1 L of the gradient have been sent through the column. The products-containing Fractions are combined and reduced to a small volume under reduced pressure constricted. Adding 100 ml of ethanol provides the desired phosphate in the form of a white powder in an amount of 1.61 g (53%) after one successive Washing with ethanol and ether and drying at 1000C for a period of time of 5 hours. F.

(Decomposition)> 160 ° C, [s] 25-27.5 (C 1.06, 0.1N NaOH), # max pH1 213 nm (# 1O 1OO), # max pH7 235 (8 75O), # max pH11 238 (7 41O), MPR (DMSO-d6) g 5.72 (d, 1, J = 4Hz, H11>, 8.08 (s, 1, C2H).

Analysis: Calculated for C11H15N408P.H2O: C 34.74, H 4.50, N 14.73 Found: C 35.21, H 4.39, N 14.98.

6-Amino-1-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate (3-deaza-5'-guanylic acid, compound 29) A solution of 1.09 g (3 mmol) of the compound 27 and 50 inl of water are brought to a pH of 10.0 with a 10% sodium carbonate solution set and refluxed for a period of 40 minutes. The healing yellow solution is then brought to a pH of 6.5 using Dowex 50 (Ht) and placed on a column packed with Bio-Rad Ag-1x8 (formate form, 50-100 mesh, 40 ml). The column is first filled with 250 ml of water and then not washed with a 0.2 to 0.5 m formic acid gradient (1 liter each). That Product appears after about 1 liter of the gradient has been sent through the column are.

The fractions containing the product are pooled, whereupon is concentrated to a small volume. The addition of 150 ml of ethanol precipitates a light beige powder that is filtered and then successively with ethanol and ether is washed.

After drying at 100 ° C for a period of 12 hours 0.49 g (45%) of the compound 29 is obtained. F. (decomposition)> 180.degree. [α] D25 - 11.4 (C 1.06 water), # maxpH1 287 nm (# 8 400), 306 (shoulder) (4 930), # macpH7 272 (8 400), 303 (6 380), # maxpH11 272 (8 130), 303 (6 090), PMR (D2Q): 5.89 (d, 1, J = 4 Hz H1,), 9.00 (1, S, C2H).

Analysis: Calculated for C1H15N4O8P: C 36.47, H 4.17, N 15.47 Found: C 36.22, H 4.29, N 15.21 Example 11 6-Amino-1-β-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate (3-deaza-5'-guanylic acid, compound 29) To a solution of 2.82 g (18.44 mmol) Phosphoryl chloride and 11.5 ml trimethyl phosphate (cooled to OOC using an ice bath), 1.3 g (4.61 mmol) of the pulverized Connection 11 given. The suspension is at 0 ° C (protected against moisture glide) stirred for a period of 10 hours. The amber solution will transferred dropwise to a flask in which 250 ml of an anhydrous ether be stirred vigorously. The ether is decanted off, whereupon another 150 ml of ether added to the beige precipitate. After stirring for a period of time The ether is decanted after 0.5 hours.

This procedure is repeated once more with a further 150 ml of ether. The precipitate is filtered off, washed with ether and then poured into about 30 g of ice water dissolved. The aqueous solution is left to stand at room temperature overnight, adjusted to a pH of 8 using an In MaOH solution and to a applied column filled with Bio-Rad-AG 1x8 (formate form, 50-100 mesh, 15 ml). After washing with 150 ml of water, the column becomes with a gradient of 0.2 m up to 0.5m formic acid (500 ml each, 15 ml fractions are collected) eluted. Fractions 20 to 75 are combined and reduced to a volume in vacuo constricted. After the addition of 150 ml of ethanol, the compound 29 precipitates filtered, washed with ethanol and ether and under a high vacuum at 1000C is dried over a period of 12 hours (0.5 g, 30%). The material is identical to compound 29, which was prepared according to Example 10.

6-Amino-3-ß-D-ribofuranosylimidazo F4,5-1 / 2 -pyridin-4 (5H) -one-5'-phosphate (Compound 30) A mixture of 564 mg (2 mmol) of powdered 6-amino-3-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one, 612 g (4 mmol) of phosphoryl chloride and 10 ml of trimethyl phosphate is at 0 ° C during stirred for a period of 3 hours. Thin layer chromatography (aliquot, hydrolyzed with water, silica gel, isopropanol / 28% ammonium hydroxide / water, 7: 1: 2) shows that a complete and unambiguous conversion of the nucleoside to the Nucleotide took place. The cold light beige solution is added dropwise to 250 ml of an anhydrous cold and stirred ether added in a flask. After a Stirring for a period of 10 minutes, the ether is decanted off. This The procedure is repeated once more with 125 ml of ether. The white precipitate is filtered, washed with ether and then dissolved in approximately ice water. The aqueous solution is brought to a pH of approx. 8.5 using sodium hydroxide adjusted and filled with Bio-Rad AG-1x8 (formate form, 50-100 mesh, 20 ml) Pillar abandoned. After washing with 500 ml of water, the column is equipped with a Gradients from 300 ml of water to 300 ml of a 1, Om formic acid eluted. The parliamentary groups which contain the product are combined and evaporated in vacuo, a crystallization from ethanol / water gives the phosphate in the form of white crystals (400 mg from two servings, 55%). F. (decomposition) ½2000C after drying at 1000C during a period of 5 hours. [α] D25 + 92.2 (C = 1, O5, H2O), UV # max pH1 227 nm (# 1O 72O), 31O nm (# 5 722), 316 nm (# 6 7oo), # max pH1 258 nm (# 5 722), 316 nm (# 6 7OO), Rf (silica gel, isopropanol / ammonium hydroxide / water, 7: 1: 2) = 0.20, Rf silica gel, Acetonitrile / 0.2m ammonium chloride, 3: 1) = 0.24.

Example 12 5-Cyanomethyl-1-β-D-ribofuranosylimidazole-4-carboxamide-3 ', 5'-cyclic Phosphate (Compound 28) A mixture of 1.5 g (4.15 mmol) of 5-cyanomethyl-1-ß-D-ribofuranosylimidazole-4-carboxamide-5'-phosphate, 1.22 g (4.15 mmol) of 4-morpholine-N, N'-dicyclohexylcarboxamidine and 100 ml of a dry one Pyridine is evaporated in vacuo. The remaining syrup will collect with further dry pyridine several times (75 ml each time) evaporated. The syrup will dissolved in 150 ml of a dry pyridine and added dropwise (over a period of time of 1 hour) through a reflux condenser into a refluxing anhydrous Solution of 4.28 g (20.75 mmol) of dicyclohexylcarbodiimide in 300 ml of dry pyridine given. f) the solution is refluxed for a further 2 hours, whereupon 50 ml of water are added. After 8 hours, the solution is evaporated in vacuo, whereupon 50 ml of water and 50 ml of ter are added to the residue. The aqueous layer is separated off, extracted with 2 x 100 ml of ether, to a pH of about 8 below Use of concentrated ammonium hydroxide discontinued and in a with Bio-Rad-AG Given a 1x8 (50-100 mesh) filled column (formate form, 40 ml). The pillar comes first with 500 ml of water and then with a gradient of 0.75m to 1.50m formic acid (each 1 1> washed. The product then appears after about 1 1 des Gradients have been sent through the column. The fractions containing the product are combined and concentrated in vacuo to a small volume. The addition of Ethanol provides the desired cyclic phosphate in the form of a beige powder in an amount of 500 mg (35%) after successive washes with ethanol and ether and drying at 100 ° C for a period of 5 hours. F. > 180 ° C. UV # max pH1 215 nm, # max pH7 234 nm, # max pH11 237 nm, Rf (silica gel, Isopropanol / ammonium hydroxide / water, 7: 1: 2) = 0.57, Rf (Kieselgen, acetonitrile / 0.2m Ammonium chloride, 3: 1) = 0.56.

6-Ammo-1-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate (Compound 31) Method A .: A solution of 5-cyanomethyl-1-ß-D-ribofuranosylimidazole-4-carboxamid-3 ', 5'-ciclischem Phosphate (compound 28) in an amount of 344 mg (1 mmol) and 25 ml of water is to a pH of 10> 0 using a 10% sodium carbonate solution set and held at reflux for 40 minutes. never yellow solution is set to a pH of 6.5 using Dowex 5O (H +) and on a column filled with Bio-Rad AG 1x8 (formate form, 50-1OO mesh, 25 ml). The column is first filled with 250 ml of water and then with a gradient of 0.75 m Washed formic acid (1 1) to 1.5m formic acid (1 1). The factions that do the Product contained @ un, are combined and concentrated in vacuo to a small volume an addition of ethanol precipitates the cyclic phosphate, which is filtered with ethanol and ether and washed in vacuo at 100 ° C for a period of 12 hours is dried.

This gives @ 15O mg (44) of the product with a D. (decomposition) > 2OO ° C. UV # max pH1 285 nm, 3O6 nm # max pH7 271 nm, 3O2 nm # pH 11 271 nm, 303 nm, Rf (silica gel, isopropol / ammonium hydroxide / max water, 7: 1: 2) = 0.44, Rf (Silica gel, acetonitrile / 0.2m ammonium chloride, 3: 1) = 0.41.

Method B.:A mixture of 1.04 mg (3.0 mmol) 6-amino-1-ß-D ribofuranosdylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate (Compound 29), 8.79 g (3 mmol) of 4-morpholine-N, N'-dicyclohexylcarboxamidine and 150 ml of a dry dimethyliormamide is evaporated in vacuo. The one left behind The syrup is evaporated several times together with further dimethylformamide (50 ml each time). The syrup is dissolved in 150 ml of dry dimethylformamide and added dropwise during a period of 1 hour through a reflux condenser into a lower Refluxing anhydrous solution of 3.09 g (15 mmol) of dicyclohexylcarbodiimide and added 250 ml of orange pyridine. The solution is for a period of refluxed for a further 2 hours, after which 100 ml of water are added. After 8 hours, the solution is evaporated in vacuo, whereupon 5O ml of water and 5O ml of ether are added to the residue. The aqueous layer is separated with ether extracted and used to a pH of about 8 of concentrated ammonium hydroxide and set on a Bio-Rad-AG-1x8 (50-100 mesh) filled formate column (35 ml).

The column is first filled with 500 ml of water and then with a gradient from 0.75m formic acid (1 1) to 1, Sm formic acid (1 l). The parliamentary groups which contain the product are poured together and in a vacuum on a small Volume constricted.

After adding ethanol, the cyclic phosphate falls in one Amount of 412 mg (currently 0%). This material is identical to mi1. according to the Method A produced cyclic phosphate.

Example 13 5-Cyanomethyl-1 (2,3-O-ispropylidene-β-D-ribofuranosyl) -imidazole-4-carboxamide (Compound 32) A solution of 1.41 g (5 mmol) of 5-cyanomethyl-1-β-D-ribofuranosylimidazole-4-carboxamide (Compound 10); 20 ml of a dry acetone and 10 ml of 2,2-dimethoxypropane is cooled in an ice bath and added 280 mg of a 70% perchloric acid touched. The ice bath is removed and the reaction is carried out with stirring at room temperature allowed to proceed for a period of 3 hours. The reddish orange colored solution is adjusted to a pH of about 7 using a 10% strength aqueous potassium hydroxide solution and evaporated in vacuo. It will obtain a syrup which is dissolved in chloroform. The solution is filtered and placed on a silica gel column filled with 45 g. An elution with chloroform / methanol (20: 1) gives 135 g (84%) of the isopropylidene derivative in the form of a white foam.

PM, R DMSO-d6): # 1.39, 1.58 (s, 3, CH3), 4.48 (s, 2, CH2), 6.00 (d, 1, H1,), J J = 2 Hz, 7.35, 7.53 (s, 1, NH), 8.14 (s, 1, C2H).

Analysis: Calculated for C14H18N405: C 57.17, H 5.63, N 17.38 Found: C 57.31, H 5.78, N 17.49 5-cyanomethyl-1- (2,3,5-tri-O-acetyl-β-D-ribofuranosyl) -imidazole-4-carboxamide (Compound 33) A suspension of 1.41 g (5 mmol) of 5-cyanomethyl-1-ß-D-ribrDfuranosylimidazole-4-carboxamide, 15 ml of acetic anhydride and 20 mg of p-dimethylaminopyridine are added at room temperature stirred for a period of 8 hours. A thin layer chromatography (Kiesselgel, CHCl3-MeOH, 4: 1) shows the presence of three products. cheerful 20th mg of p-dimethylaminopyridine and 5 ml of acetic acid hydride are added, whereupon the Stirring continued for a period of 36 hours at room temperature will. The solution is evaporated in vacuo to a syrup which is dissolved in chloroform and applied to a silica gel column (60 g). An elution with chloroform / methanol (20: 1) gives 2.0 g (95%) of the Traicetats in the form of a white foam. PMR (DMSO-d6): 2.10, 2.10, 2.16 (s, 3, COCH3), 4.40 (s, 2, CH2) 6.13 (d, 1, H1,) J = 5Hz, 7.39, 7, 58 (s, 2, NH), 8.19 (s, 1, C2H).

Analysis: Calculated for C17 H20N4O8: C 50.00, H 4.94, N 13.72 Found: C 49.91, H 5.22, N 13.36 6- (N, N-dimethylaminomethyleneamino) -1-β-D -ribofuranosylimidazo- [4,5- c] -pyridin-4 (5H) -one (Compound 34) A suspension of 564 mg (2 mmol) of 3-deazaguanosine (Compound 11), 1.19 g (10 mmol) of dimethylformamide dimethylacetal and 10 ml of dimethylformamide is heated with stirring to 80 ° C. over a period of 6 hours. The deep red Solution is evaporated in vacuo to a thin syrup, whereupon 15 ml of ethanol is added will. Then the addition of ether follows until the cloud point is reached has been. Cooling at OOC overnight gives 450 mg of brown microcrystals (washed with cold ethanol) Another 200 mg of brown micron crystals with of the same purity are obtained from a second serving. The total yield on the dimethylamibnomethylene derivative of 3-deazaguanosine is 650 mg (96 ° Õ).

Imine test sample is obtained in such a way that a part is in hot Dimethylformamide is dissolved, whereupon ether is added to the cooled solution until the cloud point has been reached. Cool to 00C overnight Licenses the desired compound in the form of yellow microcrystals. F.

243 to 245 ° C (decomposition) (after drying at 100 ° C during a period of 5 hours). [α] D25-78.9 ° C (c.1, DMF), UV # maxpH1 275 nm (shoulder) (# 13 000), 290 nm (# 14 100), # maxpH2 230 nm (# 14 000), 312 nm (# 18 650), # maxpH11 233 nm (# 13 450), 312 nm (# 18 650), PMR (DMSO-d6): # 2.98 (s, 3, CH3), 3.08 (s, 3, CH3), 5.70 (d, 1, H1,), J = 6 Hz, 6.15 (s, 1, C7H), 8.05 (s, 1), 8, 11 (s, 1), 10.7 (brs 1, NH).

Analysis: Calculated for C14H19N505: C 49.84, H 5.68, N 20.76 Found: C 49.74, H 5.72, N 20.73.

6-Acetamido-1- (2,3,5-tri-O-acetyl-β-D-ribofuranosyl) -imidazo-E4,5-cj -pyridin-4 (5H) -one (Compound 35) A mixture of 1.4 g (4.97 mmol) of 3-deazaguanosine (Compound 11), 13 ml of acetic anhydride and 20 ml of a dry pyridine stirred at room temperature for a period of 3.5 hours. The solution is evaporated in vacuo, whereupon the residue is evaporated 3 times together with water will. Recrystallization of the residue from ethanol gives beige needles in one Amount of 1.5 g (67%). F. 241 to 242 ° C (decomposition) after drying at 100 ° C for a period of 5 hours. UV # maxpH1 277 nm (# 12 700), 297 nm (# 13 400), # maxpH7 268 nm (# 13 200), 299 nm (# 12 300), # maxpH11 223 nm (# 13 700), 285 nm (# 10 800), PMR (DMSO-d6); # 1.15 (s, 9, COCH3), 6.19 (d, 1, H1,), J = 5Hz, 6.58 (s, 1, C7H), 8.25 (s, 1, C2H), 10.70 (brs, 1, NH) 11.5 (brs, 1, NH).

Analysis. Calculated for C198H22N4O9: C 50.66 H 4.92, N 12.44 Found: C 50.62 H 5.07, N 12.34 Example 14 Enzymatic preparation of 3-deazaguanosine (Compound 11) Incubation samples contained in a final volume of 1.0 ml 0.5 ml of 1m tris-HCl buffer (pH 7.5), 0.125 Inl of a 10 nM aqueous solution of Ribose-1-phosphate dicyclohexylammonium salt, 0.125 ml of a 1 mM aqueous solution of 3-deazaguanine (compound 5), 0.03 ml of an enzyme suspension (calf spleen nucleoside phosphorylase from Sigma Chemleal Co., St. Louis, Mo.) and 0.22 ml of distilled water.

The samples are incubated at 250C. The UV spectra recorded using a Cary-14 spectrophotometer, are recorded every 5 minutes determine a change in absorption. After 20 minutes there will be no more Changes noted. The value #max (pH 7.5) shifts from 262 nm to 270 nm, With an increase in the extinction coefficient, the #max, peak becomes at 298 nm (pH 7.5) one shoulder. The highest degree of conversion to the nucleoside then becomes determined when the concentration of 3-deazaguanine (compound 5) 1 x 10-4 m, the concentration of ribose-1-phosphate 3 x 10-4 4 to 1 x 10 3m and the concentration the nucleoside phosphorylase is 60 to 90 µg / ml in the reaction mixture.

U! N additionally confirm that the product thus obtained consists of 3-deazaguanosine (compound 11), the procedure is as follows. 3-Deaza zaguanine (Compound 5) is used in an amount of 4.5 mci (0.05 mmol) in 300 ml of a 0.5m tris-HCl buffer (pH 7.5) dissolved. 42.8 mg (0.1 mmol) ribose-1-phosphate dicyclohexylammonium salt and 6 mg (24 units / mg) nucleoside phosphorylase are added. The reaction mixture is stirred at 25 ° C for a period of 2 hours. The pH of the solution is adjusted to 4.5 using IICl, followed by mixing through a 1 x 3 cm activated carbon column (100-200 mesh) is sent. The column is filled with 200 ml Washed water, whereupon the product with ethanol / water / conc. NH4OH (45:45:10) in an amount of 300 ml is eluted. The eluent is brought to dryness in vacuo evaporated, leaving an amorphous light green material.

Yield: 8.1 mg (95%). Through the UV spectrum as well as through thin layer chromatography it is determined that the compound is identical to the synthetic 3-deazaguanosine (Compound 11).

In general, 3-deazaguanine (compound 5) can be enzymatically converted into the 3-deazaguanosine (compound 11) by reaction with the enzyme nucleoside phosphorylase at a pH between about 5 and about 9 and preferably 7 to 8 as well at an enzyme concentration of from about 0.05 to about 0.5 mg / ml and preferably about 0.05 to about 0.1 mg / ml and at a temperature between about 0 and about 50 ° C, with the preferred temperature range about 25 to about 35 ° C. Satisfactory results are obtained if the 3-deazaguanine in a concentration of more than 5 x 10 5m and preferably of approximately 1 x 10 m and the ribose-1-phosphate in a concentration is from about 3 x 10 4 to about 1 x 10 m. Generally are approx 0.1 to about 2 hours, and preferably about 0.5 to about 1 hour for the reaction required. The enzyme source can be derived from an animal, tissue or other consist of bacteria. The main sources of bacteria are E. coli and yeast, while there are a variety of animal sources such as beef spleen, rat liver, calf liver, Calf sweetbreads, beef liver, monkey brain, horse liver, calf's spleen, human erythrocytes, Fish skins and fish muscles. The enzyme can be a purified protein, it can are also present in actively metabolizing bacterial cells or fungal oils. Lies it then stands in actively metabolizing bacterial cells or fungal cells Expect Fermontations using these cells or mutants this cells lead to the production of 3-deazaguanosine from 3-deazaaann.

Example 1 5 In performing this example, the compounds 4, 3, 10, 11, 20, 23 and 29 tested to determine their in vitro antiviral effectiveness, the method of inhibiting the virus-induced cytopathogenic effect (CPE method) by Sidwell et al (Applied Microbiology, 22: 797-801, 1971). the CPE method consists in the antiviral agent in a cell culture medium of vitamins, Amino acids, serum, buffer, penicillin, streptomycin and an indicator dye to be suspended in water. The virus suspended in the cell culture medium becomes one prepared monolayer of KB cells or RK-13 cells is added, whereupon a equal volume of the antiviral agent is added within 15 minutes.

The infected treated cells are examined through a microscopic Investigation assessed. A comparison test is carried out for each test, only reference cells and only one cell culture medium being used, the same are virus comparison tests (cells and virus cell culture medium) and toxicity comparison tests (Cells as well as chemical and cell culture medium).

The Sidwell et al virus scoring system (VR system) described in the the above cited reference "Applied Microbiolo (jy" is described, is used to assess the level of significance of CPE inhibition. A VR value greater than 0.5 indicates significant antiviral activity is present, while a VR value of less than 0.5 shows only slight antiviral activity reflects.

The results of in vitro tests are shown in Tables I and II emerged.

Compounds 5 and 11 are also tested for their cytotoxicity tested and compared with 1-ß-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. the Results are summarized in Table III.

Table I Anti-DNA virus activity of 6-aminoimidazo 4,5-c -pyridin-4 (5H) -one as well as related connections Ver Name of connection bin- AV / 3 HSV / 1 HSV / 2 VV HCMV MCMV PRV MV application no.

5 6-Aminoimidazo [4,5-c] -pyri- 1.1 * 1.3-1.2 0.3 0.6 0.3 0.9 din-4 (5H) -one (7) + (18) (4) (1) (1) (1) (1) 11 6-Amino-1-β-D-ribofuranosyl-0.8 0.9-0.6 0.5 - 0.3 1.0 imidazo [4,5- c] pyridine-4 (5H) - (4) (13) (7) (1) (1) (1) on 29 6-amino-1-β -D-ribofuranosyl- 0.9 1.0 0.7 imidazo [4,5-c] -pyridine-4 (5H) - (3) (2) (2) one-5'-phosphate 4 4 (5) -cyanomethylimidazo- 0.8 0.9 5 (4) -carboxamide (2) (6) 10 5-cyanomethyl-1-β-D-ribo-0.6 1.3 furanosylimidazo-4-carboxamide (3) (1) 27 5-cyanomethyl-1-ß-D-ribofurano- 0.8 0.5 0.3 sylimidazo-4-carboxamide-5'- (2) (2) (2) phosphate 20 6-Amino-3- (tetrahydropyran-2- 0.8 yl) -imidazo [4,5-c] -pyridine- (1) 4 (5) -one 23 6-Amino- (5'-deoxy-ß-D-ribofu0.9 ranosyl) -imidazo [4,5-c] -pyridine- (2) 4 (5H) -on * virus rating + indicates the number of tests virus identification: AV / 3: adenovirus, type 3, HSV / 1: herpes simplex virus, type 1; HSV / 2: Herpres simplex virus, Type 2, VV: vaccinia virus, HCMV: human cytomegalovirus, MCMV: mouse cytomegalovirus, PRV: pseudorabies virus, MV: myxoma virus.

Table II Anti-RNA viral activity of 6-aminoimidazo [4,5-c] pyridin-4 (5H) -one as well as related connections Ver Designation of the connection bin- PIV / 3 PIV / 1 RV / 1A RV / 2 RV / 8 RV / 13 RV / 30 RV / 56 IV / Ao VSV application no.

5 6-Aminoimidazo [4,5-c] - 1.0 * 1.0 0.3 1.3 1.3 1.2 0.3 1.1 0.5 1.3 pyridin-4 (5H) -one (9) + (1) (3) (3) (3) (10) (3) (3) (7) (1) 11 6-amino-1-ß-D- ribofura- 0.6 0.6 0.1 1.2 1.2 1.0 - 0.7 0.1 1.1 nosylimidazo [4,5-c] -pyri- (6) (1) (2) (2 ) (2) (11) (2) (5) (1) din-4 (5H) -one 29 6-amino-1-β-D-ribofurano-0.8 0.3 0.9 sylimidazo [4.5 -c] -pyri- (3) (1) (3) Din-4 (5H) -one-5'-phosphate 4 4 (5) -cyanomethylimide-0.5 0.6 azole-5 (4) -carboxamide (4) (4) * Virus rating + indicates the number of tests Virus identification: PIV / 3: parainfluenza virus, type 3, PIV / 1: parainfluenza virus, type 1, RV / 1A: rhinovirus, Type 1A, RV / 2: rhinovirus, type 2, RV / 8: rhinovirus, type 8, RV / 13: rhinovirus, type 13, RV / 30: rhinovirus, type 30, RV / 56: rhinovirus, type 56, IV / Ao: influenza virus, Type Ao, VSV: bladder stoamtitis virus.

Table III Cytotoxicity of 3-deazaguanine and 3-deazaguanosine compared to 1-ß-D-ribofuranosyl-1,2,4-triazole-3-carboxamide conn-conn-1 -ß-D-kibofuranosyldung 5 dung 11 1,2,4-triazole-3-carboxamide cytotoxicity * - KB cells 1.0 1.0 3.2 Cytotoxicity - RR13 cells 1.0 10.0 Cytotoxicity - chick embryo 3.2 3.2 cells * Cytotoxicity is expressed as the dose that does not contain any visible changes in the cells caused, which microscopically after a 72 hours of exposure to the compound at 370C. KB cells: Human adenocarcinoma of the nasopharynx, RK-13 cells: continuous Continuous passage rabbit kidney. Chicken embryo cells: primary Cells derived from minced 9 day old chicken embryos.

Example 16 3-deazaguanine is further opposed to its effectiveness Influenza A2 virus tested while conducting an animal experiment. To carry out In this study, female Swiss webster mice weighing 16 to 17 g are light anesthetized and intranasally at a 75% lethal dose (LD75) of the Japan 305 strain infected by influenza A2 viruses. Be 15 minutes before allowing the virus to act the mice intraperitoneally with 3-deazaguanine or 1-ß-D-ribofuranosyl-1,2,4-triazole-3-carboxamide under Adherence to different doses of each active ingredient, suspended in a sterile physiological saline solution. DUe virus comparison smiiuse are only with the saline solution, while the toxicity comparison animals with the respective Dosages of each active ingredient are treated, but only a sham infection be subjected. The animals are observed for a period of 21 days, the deaths occurring during this period being recorded daily will. The results of this investigation are summarized in Table IV, from which it can be seen that both compounds have a significant anti-influenza virus effect exhibit.

Table IV Effect of a single intraperitoneal injection of 3-deazaguanine or 1-ß-D-ribofuranosyl-1,2,4-triazole-3-carboyxamide on influenza A2 virus infections in mice active ingredient dose- toxic- survival- mean survival time, increase, increase in survival, increase in mg / kg comparison pb life-timec pd survival- Survival- (days) de / total dea / total 3-deazaguanine 400 0/5 1/10 - 0.3 0.05 (compound 5) 200 3/5 2/10 - 9.7 0.05 100 5/5 5/10 0.1 9.0 0.05 1-ß-D-Ribofu 800 5/5 1/10 - 9.0 0.05 ranosyl-1,2,4- 400 5/5 2/10 - 11.4 0.01 triazole-3-carb- 200 5/5 4/10 0.2 9.3 0.05 oxamide saline - - 4/20 - 7.8 -a The survivors on day 21 b Probability (chi-square analysis) c Animals that were on or before the 21st day die d probability (t-test) Example 17 To carry out In this example, compound 5 is tested for its anti-tumor activity in mice. The compounds 5 proves to be in one against Hela and L1210 cells Tissue culture as cytotoxic. A 10-5 m concentration of compound 4 causes a 50% inhibition of the incorporation of 3H-thymidine and 3H-uridine into the acid-insoluble Fraction of L1210 cells in the tissue culture. Table V shows that in the L1210 leukemia system compound 5 (LD10 500 mg / kg) with a dosage of 8i. p injections) of 20 mg / kg (qd, 1-9), 40 mg / kg (qd, 1-9) and 80 mg / kg (qd, 1-9) the life span in female BDF1 mice increased by 32, 43 and 63 90, respectively. Ara-C (cytosine arabinoside) is tested as a standard.

Compound 5 yields at a dosage (i.p. injections) of 40 mg / kg (qd, 1-7) also show a 75% and 93% inhibition of growth of subcutaneous implantations of adenocarcinoma 755 in C57 Blk / 6 female mice.

Table V Activity of compound 5 against leukemia L1210 in female EDF1 mice treatment, (i.p.) means of. T / C survivors, weight, Tagc g Vei eich, saline 8, 2 2, 2 solution compound 5 sn mg / kg, qd (1-9 10.83 +2.0 1.32 (0/6) 40 mg / kg, qd (1-9) 12.00 +0.4 1.43 (1/6) 80 mg / kg, qd (1-9) 13 , 33 +1.7 1.63 (0/6) Ara-C 40 mg / kg, qd (1-9) 17.33 -0.2 2.11 (0/6) All animals will i.p. inoculated with 10 leukemia cells. The conversion takes place 24 hours after the Inoculation. The values in brackets indicate the survivors after 21 days.

It can be seen from Examples 15 and 16 that 3-deazaguanine (compound 5) and 3-deazaguanosine (Compound 11) show a broad spectrum of antiviral activity and are particularly effective against viruses that cause respiratory disease cause. In view of the close structural similarity to 3-desazagua, nin and 3-deazaguanosine as well as the usual increased solubility of the salts of active pyridine compounds the acid addition salts can be expected to also have antiviral activity exhibit.

Compounds 5 and 14 have been shown to have one antibacterial activity in vitro against E. coli (gram negatives) and Staphylococcus aureus (gram-positive), while compound 23 has an effect on Staphylococcus aureus (gram-positive) shows.

The compounds according to the invention also have other medical ones Properties.

Claims (1)

Claims 1. Compound of the formula: where X is> NH, -NH2 or -OCH3, Y>CNHR,> CNR1 or -C = N, where @ is H or acyl and R1 = CH-N (CH3) 12, ZH, tetrahydropyranyl, ß- D-ribofuranosyl, 5-deoxyß-D-ribofuranosyl, ß-D-ribofuranosyl-5-phosphate, 5-D-ribofuranosyl-3,5-cyclic phosphate, C1-C18-acyl and isopropylidene-ß-D-ribofuranosyl, C1 -C18-acyl and isopropylidene-5-deoxy-ß-D-ribofuranosyl, C1-C18-acyl and isopropylidene-ß-D-ribofuranosyl-5-phosphate or C1-C18-ß-D-ribofuranosyl-3,5-cyclic Phosphate is, as well as its physiologically acceptable salts, with the proviso that X mir> NH and Y> CNHR or 5 CNR1, when X and Y are connected to one another, and X is only -NH2 or -OCH and Y is only -CN, when X and Y are not linked. 2. Compound according to claim 1 of the formula: where Z is H, tetrahydropyranyl, ß-D-ribofuranosyl, 5-deoxyß-D-ribofuranosyl, ß-D-ribofuranoxyl-5-phosphate or ß-D-ribofuranosyl-3,5-cyclic phosphate, as well as C1 -C18 Acyl, isopropylidene and dimethylaminomethylene derivatives and physiologically acceptable salts thereof. 3. A compound according to claim 2, characterized in that Z is for ß-D-ribofuranosyl-5-phosphate. 4. A compound according to claim 2, characterized in that Z is for 5-deoxy-ß-D-ribofuranosyl is 5. A compound according to claim 2, characterized in that that Z stands for ribofuranosyl-3,5-cyclic phosphate. 6. A compound according to claim 2, characterized in that Z is for Tetrapyranyl stands. 7. A compound according to claim 2, characterized in that Z is hydrogen means. 8. A compound according to claim 2, characterized in that Z is for β-D-ribofuranosyl stands. 9. A compound according to claim 1 of the formula: wherein X is -NH2 or -OCH3, ZH, tetrahydropyranyl, ß-D-ribofuranosyl, 5-deoxy-ß-D-ribofuranosyl, ß-D-ribofuranosyl-5-phosphate, ß-D-ribofuranosyl-3,5- cyclic phosphate, C1-C18-acyl and isopropylidene-ß-D-riboufranosyl, C1-C18-acyl and isropylidene-5-deoxy-ß-D-ribofuranosyl-5-phosphate and C1-C18-acylribofuranosyl-3,5-cyclic Phosphate is as well as the physiologically acceptable salts thereof. 1 0. A compound according to claim 9, characterized in that X is for NII2 is and Z is tetrapyranyl. 11. A compound according to claim 9, characterized in that X and NH2 and Z is hydrogen. 12. A compound according to claim 9, characterized in that X is for NH2 and Z is ß-D-ribofuranosyl. 1 3. A compound according to claim 9, characterized in that X is for NH2 and Z is ß-D-ribofuranosyl-5-phosphate. 14. A compound according to claim 9, characterized in that X is for NH2 and Z is ß-D-Rihofuranosyl-3,5-phosphate. 15. A compound according to claim 9, characterized in that X is for NH2 and Z is 5-deoxy-ß-D-ribofuranosyl. 16. Compound nach'Anspruch 9, characterized in that X for OCH3 is and Z is tetrahydropyranyl, ß-D-ribofuranosyl, ß-D-ribofuranosyl-5-phosphate, ß-D-ribofuranosyl-3,5-cyclic phosphate and 5-deoxy-ß-D-ribofuranosyl, as well C1-C18 acyl and isopropylidene derivatives and physiologically compatible salts thereof. 17. 6-Amino-3- (5-phosphoryl-β-D-ribofuranosyl) -imidazo [4,5-c3-pyridine-4 (5H) -one. 18. 6-Amino-3- (β-D-ribofuranosyl) -imidazo [4,5- c] -pyridin-4 (511) -one 19. 6-Amino-1- (5-phosphyl-β-D-ribofuranosyl) -imidazo [4,5- c] -pyridin-4 (5H) -one. 20. 6-Amino- (β-D-ribofuranosyl) -imidazo [4,5- c] -pyridin-4 (5H) -one. 21. 6-Amino-1- (3,5-cyclic phosphoryl-β-D-ribofuranosyl) -imidazo- [4,5- c] -pyridin-4 (5H) -one. 22. 6-Aminoimidazo [4,5- c] pyridin-4 (5H9-one. 23. Process for the preparation of 6-aminoimidazo [4,5-c] -pyrimidin-4 (5) -one (deazazaguanine), characterized in that methyl-4 (5) -acetamido-2-imidazole-5 (4) -carboxylate under reflux conditions with a dehydrating agent to recover 4 (5) -Cyanomethylimidazole-5 (4) -carboxylate is reacted, such a cyanomethylllyl compound to a temperature of about 100 to about 1500C in the presence of liquid Ammonia is heated to obtain 4 (5) -cyanomethylimidazole-5 (4) -carboxamide and then such a cyanomethylcarboxamide in the presence of an alkali metal carbonate is subjected to a reflux treatment to obtain 3-deazaguanine. 24. The method according to claim 23, characterized in that the cyanomethyl carboxylate with NH4Cl in an aliphatic alcohol and in the presence of ammonia in a Temperature from about 100 to about 1500C for the recovery of 3-deazaguanine is treated. 25. Process for the preparation of 6-amino-1-β-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5) -one (3-deazaguanosine), characterized in that that 4-deazaguanine with the enzyme nucleoside phosphorylase in the presence of ribose-1-phosphate in a pH from about 5 to about 9 and at a temperature of about 0 up to 50 ° C. 26. The method according to claim 25, characterized in that the used Enzyme is present at a concentration of from about 0.05 to about 0.5 mg / ml. 27. The method according to claim 26, characterized in that the enzyme is used at a concentration of from about 0.05 to about 01 mg / ml. 28. The method according to claim 26, characterized in that the 3-deazaguanine at a concentration of at least about 5 x 10 m and that has ribose-1-phosphate is used at a concentration of about 3 x 10-4 to about 1 x 10-3. 29. The method according to claim 28, characterized in that the pH between about 7 and about 8 and the temperature between 25 and about 350C. 30. Process for the preparation of 6-amino-1- (Z) -imidazo [4,5-c] -pyridin-4-one or 6-Amino-3- (Z) -imidazo [4,5-c] -pyridin-4-one, where Z is ß-D-ribofuranosyl or 5-Deoxy-ß-D-ribofuranosyl, characterized in that 3-deazaguanine by Reaction with hexamethyldisilazane is silylated under reflux conditions, whereupon the silylated 3-deazaguanine produced in this way is further protected with C1-C8 acyl-protected Ribofuranosyl or 5-deoxyribofuranosyl halide in the presence of a non-thydroxylated one Solvent is implemented. 31. The method according to claim 30, characterized in that the silylation stage is carried out in the presence of ammonium sulfate as a catalyst. 32. The method according to claim 30, characterized in that the used n non-hydroxylated solvent consists of acetonitrile and the further reaction stage is carried out at a temperature of about 20 to about 25 ° C. 33. Process for the preparation of G-amino- (Z) -imidazo [4,5-c] -pyridin-4-one as well as 6-amino-3- (Z) -imidazo [4,5-c] -pyridin-4-one, where Z is ß-D-ribofuranosyl cder 5-f) esoxy-ß-D-ribofuLallc syl, characterized in that in a first Stage methyl 4 (5) -cyanomethylimidazole-5 (4) -carboxylate with a protected ribofuranose or 5 - deoxyribofuranose in the presence of an acidic catalyst at a temperature from about 1600C to about 2000C to form 4-methoxycarbonyl-1 - (protected in Z) -imidazole-5-acetonitrile and 5-methoxycarbonyl-1- (protected Z) -imidazole-4-acetonitrile is reacted, whereupon the products of the first reaction stage in a second reaction stage reacted with ammonia at about 200C to about 1500C. 34. The method according to claim 33, characterized in that the used acidic catalyst consists of chloroacetic acid or bis (p-nitrophenyl) phosphate and the temperature is about 160 to about 1900C. 35. The method according to claim 33, characterized in that the ammonia used as liquid ammonia or as a solution in an aliphatic alcohol will. 36. Process for the preparation of 6-amino-1- (Z) -imidazo [4,5-c] -pyridin-4-one and 6-Amino-3- (Z) -imidazo [4,5-c] -pyridin-4-one, where Z is ß-D-ribofuranosyl, 5-deoxy-ß-D-ribofuranosyl or tetrahydropyranyl, characterized in that that in a first reaction stage methyl 4 (5) -cyanomethylimidazole-5 (4) -carboxalate with hexamethyldisilazane at reflux temperature to form a silylated Product is implemented, the silylated product in a second reaction stage with a C1-C8 acyl-protected ribofuranose or 4-deoxyribofuranose or dihydropyran in the presence of a Lewis acid catalyst and a non-hydroxylated solvent at a temperature of about 200C to the reflux temperature to form of methyl 5-cyanomethyl-1- (Z) -imidazole-4-carboxylate and methyl-4-cyanomethyl-1- (Z) -imidazole-5-carboxylate is reacted, in a third reaction stage the products of the second reaction stage reacted with ammonia and isolated or the products in a fourth reaction stage the third reaction stage are made to react with a weak base. 37. The method according to claim 36, characterized in that the used Lewis acid catalyst made from tin (1V) chloride and the solvent used consist of 1,2-dichloroethane and the selected temperature between about 20 and is about 250C. 38. The method according to claim 36, characterized in that the first Reaction stage is carried out in the presence of ammonium sulfate as a catalyst. 39. The method according to claim 36, characterized in that the ammonia in the form of liquid ammonia or in a solution with an aliphatic alcohol is used. 40. The method according to claim 36, characterized in that the used weak base consists of sodium carbonate. 41. Process for the preparation of 6-amino-1- (Z) -imidazo [4,5-c] -pyridin-4-one and 6-Amino-3- (Z) -imidazo [4,5-c] -pyridin-4-one, where Z is ß-D-ribofuranosyl or 5-Desosy-ß-D-ribofuranosyl, characterized in that in a first reaction stage Methyl 4 (5) -cyanomethylimidazole-5 (4) -carboxylate with llexamethyldisi] azane in the The reflux temperature is reacted with the formation of a silylated product, in a second reaction stage with the silylated product obtained in this way a C1-C8 acyl protected ribofuranosyl or 5-deoxyribofuranosy] halide in the presence of a non-hydroxylated solvent 5 at about 200C up to the reflux temperature to form methyl 4-cyanomethyl-1- (Z) -imidazole-5-carboxylate and methyl 5-cyanomethyl-1- (Z) -imidazole-4-carboxylate is reacted and in a third reaction stage the products of the second reaction stage with Ammonia can be reacted and isolated at about 200 ° C. to about 1500 ° C. or be reacted in a fourth reaction stage with a weak base. 42. The method according to claim 41, characterized in that the first Reaction stage is carried out in the presence of ammonium sulfate as a catalyst. 43. The method according to claim 41, characterized in that the in the second reaction stage used solvent consists of acetonitrile, while the temperature is about 20 to about 250C: 44. Procedure according to claim 41, characterized in that the ammonia is in the form of liquid Ammonia or in solution in an aliphatic alcohol is used. 45. The method according to claim 41, characterized in that the used weak base consists of sodium carbonate. 46. Process for the preparation of 6-amino-1-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate, 6-Amino-3-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate and 5 (4) -cyanomethyl-1-ß-D-ribofuranosylimidazo-4 ( 5) -carboxamide-5'-phosphate, characterized in that in a first reaction stage 6-amino-1-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4- (5H) -one, 6-Amino-3-β-D-ribofuranosylimidazo [4,5-c] -pyridin-4- (5H) -one or 5 (4) -cyanomethyl-1-β-D-ribofuranosylimidazole-4 (5) -carboxamide Protected against moisture and with phosphoryl chloride in trimethylphosphate are reacted at about -20 to about 30OC, in a second reaction stage the products of the first stage with formation of 6-amino-1-ß-D-ribofuranosylimidazo- [4,5-c] -pyridin-4 (5H) -one-5'-phosphate, 6-Amino-3-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate or 5 (4) -cyanomethyl- 1 -β-D-ribofuranosylimidazole-4 (5) -carboxamide-5'-phosphate are hydrolyzed, these products being isolated or, in a third stage, 5 (4) -cyanomethyl-1-β-D-ribofuranosylimidazole-4 (5) -carboxamide-5'-phosphate with a weak base to form 6-amino-1 -β-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate or 6-amino-3-β-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate is treated. 47. Process for the preparation of 6-amino-1 -? - D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate, 6-amino-3-β-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate or 5 (4) -cyanomethyl-1-ß-D-ribofuranosylimidazo-4 (5) -carboxamide-3 ', 5'-cyclic Phosphate, characterized in that in a first reaction stage 6-amino-1-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate, 6-Amino-3-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-5'-phosphate or 5 (4) -cyanomethyl-1-ß-D-ribofuranosylimidazo-4 ( 5) -carboxamide-5'-phosphate be converted into the salt of the 5'-phosphate, in a second reaction stage that Product of the first stage reaction with dicyclohexylcarbodiimide in pyrimidine at approximately Room temperature to reflux with formation of 6-amino-1-ß-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate, 6-amino-3-β-D-ribofuranosylimidazo [4,5-c] -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate or 5 (4) -Cyanomethyl -1 -ß-D-ribofuranosyl imida zo -4 (5) -carboxamid-3 ', 5'-cyclic phosphate is treated, whereby these compounds are isolated or in a third stage 5 (4) -cyanomethyl-1-β-D-ribofuranosylimidazole-4 (5) -carboxamid-3 ', 5'-cyclic Phosphate with a weak base to form 6-amino-1-ß-D-ribofuranosyimidazo [4,5-c] -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate or 6-amino-3-n-D-ribofuranosylimidazo 4,5-c -pyridin-4 (5H) -one-3 ', 5'-cyclic Phosphate is treated.