WO1990008147A1

WO1990008147A1 - Purine nucleosides, process for producing them, and drugs containing these compounds

Info

Publication number: WO1990008147A1
Application number: PCT/EP1990/000059
Authority: WO
Inventors: Alfred Mertens; Harald Zilch; Bernhard Koenig; Edith Koch
Original assignee: Boehringer Mannheim Gmbh
Priority date: 1989-01-14
Filing date: 1990-01-11
Publication date: 1990-07-26
Also published as: AU4951490A; PT92862A; IL93001A0; KR910700256A; ZA90218B; DE3900964A1

Abstract

Compounds of formula (I), in which R1 is hydrogen or the amino group, R2 is a halogen atom, a C1-C6-alkyl, C2-C6-alkenyl, C1-C6-alkoxy, C3-C6-cycloalkyl-C1-C6-alkoxy, C3-C8-cycloalkyloxy, C3-C8-cycloalkylthio, C1-C6-alkylthio group, a substituted amino group, an aryl, aralkyl, aryloxy, aralkoxy, arylthio, aralkylthio or hetarylthio group, or a heterocyclic ring, R3 is hydrogen or the amino group, R4 is hydrogen, aliphatic C1-C4 acyl or a mono-, di- or triphosphate group; their tautomers; their physiologically acceptable salts of inorganic and organic acids and bases; process for producing them; and antiviral drugs containing these compounds.

Description

Purine nucleosides, processes for their preparation and medicaments containing these compounds

The invention relates to substituted 2 ', 3'-dideoxy-2', 3'-didehydropurin nucleosides, processes for their preparation and medicaments which contain these compounds.

The present invention relates to nucleosides and nucleotides of the general formula I

in the

R _{1 represents} a hydrogen atom or an amino group,

R _{2 is} a halogen atom; a C ₁ -C ₆ alkyl; C ₂ -C ₆ alkenyl;

C ₁ -C ₆ alkoxy-; C ₃ -C ₆ cycloalkyl-C ₁ -C ₆ alkoxy-; C ₃ -C ₈ cycloalkyloxy-; C ₃ -C ₈ cycloalkylthio-; C ₁ -C ₆ alkylthio group; or an amino group R ₅ R ₆ N-, in which one of the radicals R ₅ or R ₆ can denote a hydrogen atom, otherwise R ₅ and R _{6 can be the} same or different and independently of one another a C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, C ₁ -C ₆ alkoxy, hydroxyC ₁ -Cg alkyl, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkylC ₁ -C ₆ alkyl , C ₃ -C ₈ -cycloalkenyl-C ₁ -C ₆ -alkyl-, C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl-, di-C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl-, C ₁ -C ₆ -alkoxycarbonyl-C ₁ -C ₆ -alkyl, aryl, aryl-C ₁ -C ₆ -alkyl or hetaryl-C ₁ -C ₆ -alkyl group; or an aryl, Ar-C ₁ -C ₆ alkyl, aryloxy, Ar-C ₁ -C ₆ alkyloxy, arylthio, Ar-C ₁ -C ₆ alkylthio or

Hetarylthio group; and the "aryl" and "hetaryl" parts in all the aforementioned cases of the aryl- or hetaryl-bearing groups one or more times by hydroxy, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy , Trifluoromethyl, amino or halogen groups can be substituted; or a saturated, unsaturated or aromatic heterocyclic ring with one oxygen atom and / or one sulfur atom and / or one or two nitrogen atoms and 3-7 carbon atoms, this ring being substituted by one or more hydroxy, C ₁ -C ₆ alkyl, halogen - or C ₃ -C ₆ cycloalkylthio radicals can be substituted;

R _{3 is} hydrogen or the amino group and

R ₄ denotes hydrogen or a C ₁ -C ₆ alkylcarbonyl or a mono-, di- or triphosphate group, their optically active forms, tautomers or physiologically acceptable salts of inorganic and organic acids and bases with the exception of the compounds 6-methylamino2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-ribofuranoyl-purine, 6-dimethylamino- 2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-ribofuranoyl-purine and 6-methylthio-2 ', 3'-dideoxy-2', 3'didehydro-9-ß-ribofuranoyl-purine , as well as processes for their preparation and containing these compounds

Drug.

Since the compounds of general formula I contain asymmetric carbon atoms, are also the subject of

Invention the optically active forms and racemic

Mixtures of these compounds.

The compounds of the present invention have valuable pharmacological properties. They are particularly suitable for the therapy and prophylaxis of infections caused by DNA viruses such as e.g. the herpes simplex virus, the cytomegalovirus, papilloma viruses, the varicella zoster virus or Epstein-Barr virus or RNA viruses such as toga viruses or in particular retroviruses such as the onko viruses HTLV-I and II, and the lentiviruses Visna and human immunodeficiency virus HIV-1 and 2.

The compounds of the formula I appear to be particularly suitable for the treatment of the clinical manifestations of retroviral HIV infection in humans, such as persistent, generalized lymphadenopathy (PGL), the advanced stage of the AIDS-related complex (ARC) and the clinical picture of AIDS.

It has now been found that compounds of the general formula I are particularly suitable for inhibiting the multiplication of DNA or RNA viruses at the level of virus-specific DNA or RNA transcription. The substances can influence the multiplication of retroviruses specifically by inhibiting the enzyme reverse transcriptase (cf. Proc. Natl. Acad. Sci. USA 83, 1911, 1986 and Nature 325, 773, 1987). Of particular therapeutic interest is the inhibitory effect on the HIV virus, the cause of the immune deficiency disease AIDS. Only 3'-azido-3'-deoxythymidine (German patent application DE-A-3,608,606) is currently approved for the treatment of AIDS in AIDS patients. However, toxic side effects of 3'-azido-3'-deoxythymidine on the bone marrow require blood transfusions in about 50% of the patients treated. The compounds of the general formula I do not have these disadvantages. They have an antiviral effect without being cytotoxic in pharmacologically relevant doses.

The compounds of the present invention and their pharmaceutical preparations can also be used in combination with other medicaments for the treatment and prophylaxis of the above-mentioned infections. Examples of these further drugs include agents that can be used for the treatment and prophylaxis of HIV infections or diseases accompanying this disease, such as 3'-azido-3'-deoxythymidine, 2 ', 3'-dideoxynucleosides such as 2', 3'-dideoxycytidine , 2 ', 3'-dideoxyadenosine and 2', 3'-dideoxyinosine, acyclic nucleosides (e.g. acyclovir), interferons such as A-interferon, renal excretion inhibitors such as probenicide, nucleoside transport inhibitors such as dipyridamole, as well as immunomodulators such as interleukin II or stimulation factors such as the granulocyte-macrophage colony factor. The compounds of the present invention and the other medicament can each be administered individually, simultaneously, if appropriate in a single or two separate formulations or at different times, so that a synergistic effect is achieved. Some compounds similar to general formula I that are not encompassed by the present invention are known as drugs. US Pat. No. 3,817,982 claims purine nucleosides which are substituted in the 6-position by methylamino, dimethylamino or methylamino. Furthermore, EP-A-0,286,425 purine-9-β-D-2 ', 3'-dideoxyribofuranoside are known, which can be used for the treatment of HIV infections. Mitsuya et al. (Proc. Nat. Acad. Sci. USA 82, 7096, 1985), Baizarini et al. (Mol. Pharm. 32, 162, 1987) and DeClercq et al. (Biochem. Pharm. 37, 1317, 1988) 9-β-D-2 ', 3'-dideoxy-2', 3'-didehydroribofuranoside derivatives of adenine, 2,6-diaminopurine and 7-deaza-adenine a positive effect against the HIV virus in vitro. Furthermore, the compound 6-methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-ribofuranosyl-purine (Biochem. Pharm. 37, 3543, 1988) is already known from the literature with a similar effect.

Further desazapurin nucleosides are described in EP-A-0,286,028 for nucleic acid sequencing and as antiviral agents.

Compared to the known compounds, the compounds according to the invention have an increased activity. In particular, studies on pharmacological activity found that these compounds inhibit virus replication in HIV-infected human fetal lung cells at lower concentrations than the known compounds.

Compounds of the general formula I are, for example, those in which

R _{1 represents} hydrogen or the amino group,

R ₂ halogen (eg chlorine); C ₁ -C ₆ alkoxy (e.g. propyloxy or isopropyloxy), which may be substituted by C ₃ -C ₆ cycloalkyl (e.g. cyclopropylmethoxy); C ₃ -C ₈ cycloalkyloxy (e.g. cyclobutyloxy or cyclopentyloxy); Aryloxy (e.g. phenyloxy), aralkyl (e.g. benzyl) or aralkyloxy (e.g. benzyloxy), their aryl radical can be substituted by hydroxy, C ₁ -C ₆ alkyl (eg methyl) or halogen; C ₃ -C ₆ cycloalkylthio; C ₁ -C ₆ alkylthio; Arylthio (for example phenylthio) or aralkylthio (for example benzylthio), the aryl radical of which can be substituted by hydroxyl, C ₁ -C ₆ alkyl (for example methyl) or halogen, or R _{2 is} a saturated, unsaturated or aromatic heterocyclic ring with a Oxygen atom and / or a sulfur atom and / or one or two nitrogen atoms and C ₃ -C ₇ carbon atoms (eg piperidino, pyrrolidino or furyl) and that in the ring by one or more

Hydroxy, C ₁ -C ₆ alkyl (eg methyl), halogen, C ₃ -C ₆ cycloalkylthio or aralkylthio radicals (eg benzylthio), which are optionally in the aryl radical hydroxy, C ₁ -C ₆ alkyl (eg methyl) or halogen wear, may be substituted, means, or R _{2 is} an imidazolylthio group in which the imidazole residue with C ₁ -C ₃ alkyl and / or C-substituted with nitro, or R _{2 is} an amino group which is mono- or disubstituted is by C ₁ -C ₆ alkyl (e.g.

Methyl, ethyl or isobutyl), C ₁ -C ₆ alkoxy (e.g.

Methoxy), hydroxy-C ₁ -C ₆ alkyl (e.g. hydroxyethyl) and / or C ₃ -C ₆ cycloalkyl (e.g. cyclopropyl or cyclopentyl); Aryl (e.g. phenyl) or aralkyl (e.g. benzyl), the aryl radical of which may be substituted by hydroxy, C ₁ -C ₆ alkyl (e.g. methyl) or halogen, or allyl which may be substituted by one or more C ₁ -C ₆ alkyl (e.g. Dimethyl-allyl) or C ₁ -C ₆ alkoxy groups (eg methoxyallyl) can be substituted.

R ₃ preferably represents a hydrogen atom.

The aforementioned "alkyl" parts in the various definitions can be straight-chain or branched and contain 1-6, preferably 1-4 carbon atoms, such as, for example, the methyl, ethyl, n-propyl, i-propyl, iso-butyl or tert-butyl group. In this sense, the following groups are suitable, for example, for R ₂ : the methyl, methoxy, ethoxy, methylthio, dimethylamino, allylamino, gamma, gamma-dimethylallylamino, hydroxymethylamino, hydroxypropylamino, t-butylamino , i-Propylamino, i-butylamino or ethoxycarbonylmethylamino group.

The cycloalkyl parts of the cycloalkyl, cycloalkoxy, cycloalkylthio or cycloalkenyl groups can contain 3-8, preferably 3-6 carbon atoms, such as the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group. In this sense, the following groups are suitable, for example: A cyclopropyl-methyl-amino or cyclopentyl-methyl-amino group.

In the definition of R ₂ , the amino group is mono- or disubstituted, but preferably simply by C ₂ -C ₆ alkyl, C ₂ -C ₆ alkenyl, alkoxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenylalkyl, alkoxyalkyl, Di-alkoxyalkyl, alkoxycarbonyl-alkyl, arylalkyl or

Hetarylalkyl groups, it being possible for the alkyl parts of the groups mentioned in each case to contain 1-6, preferably 1-4, carbon atoms.

For the group R ₅ R ₆ N-, preference is given to compounds in which R ₅ and R _{6 are} simultaneously a C ₁ -C ₆ alkyl group, or R5 is a hydrogen atom and R _{6 is} a C ₂ -C ₆ alkyl group. , C ₁ -C ₆ alkoxy, C ₂ -C ₆ alkenyl, hydroxyalkyl, cycloalkyl, cycloalkyl-alkyl, cycloalkenyl-alkyl, alkoxyalkyl, di-alkoxy-alkyl, alkoxycarbonyl-alkyl, Arylalkyl or hetarylalkyl group, such as a furanylmethyl, thienylmethyl or pyridylmethyl group.

Aryl is to be understood as meaning aromatic residues with 6-14 carbon atoms, such as phenyl or naphthyl. “Hetaryl” parts in all of the aforementioned hetaryl-bearing groups are understood to mean heteroaromatic radicals having one or two nitrogen atoms and a ring size of 5-7 atoms, such as pyridinyl, pyrimidinyl, furanyl or thienyl.

The saturated, unsaturated or heterocyclic rings with an oxygen atom and / or a sulfur atom and / or one or two nitrogen atoms are, for example, the morpholine, piperidine or piperazine ring.

In the event that the previously defined aryl, hetaryl or heterocyclic rings are substituted, they can be substituted once, twice or even three times, but preferably once. The groups hydroxyl, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, trifluoromethyl or come as substituents for the aryl parts or hetaryl parts

Halogen in question, the ones already mentioned

Alkyl parts represent preferred embodiments.

Halogen is to be understood as fluorine, chlorine or bromine, but especially chlorine.

In the event that the aforementioned groups contain an alkyl group as a bridge member, such as in the case of cycloalkyl "alkyl", alkoxy "alkyl", alkoxycarbonyl "alkyl", aryl "alkyl" or hetaryl "alkyl" group, here is a C ₁ -C ₃ alkyl group, especially the

Methylene group, preferred. In this sense, for example, the phenylmethyl (benzyl), cyclopropylmethyamino, thienylmethyl or pyridylmethyl group are suitable. If the alkyl parts contain additional substituents, such as in the case of the hydroxy-C ₁ -C ₆ -alkyl group, cycloalkyl-C ₁ -C ₆ -alkoxy, cycloalkyl-C ₁ -C ₆ -alkyl, etc., these substituents (in the the above examples, the hydroxy and cycloalkyl group) are at any position on the alkyl part, that is in the 1-, 2-, 3-, 4-, 5- or 6-position. Often, however, they are in each case at the terminal position of the respective alkyl part.

In the event that R2 represents a heterocyclic ring, this can have a hetero atom or a

Carbon atom bound to the purine system. The imidazole group can thus be bonded to the 6-position of the purine ring, for example, via a nitrogen atom or via a carbon atom, for example in the 1-, 2- or 4-position.

For the purposes of the present invention, the following substituents are possible, for example, as preferred embodiments:

R _{1 represents} a hydrogen atom or the amino group,

R _{2 is} a C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, one is simply a C ₂ -C ₆ alkyl, C ₂ -C ₆ alkenyl, hydroxy C ₁ - C ₄ -alkyl-, C ₃ -C ₆ -cycloalkyl-, C ₃ -C ₆ -cycloalkyl-C ₁ -C ₄ -alkyl-, C ₁ -C ₄ -alkoxy-carbonyl-C ₁ -C ₄ -alkyl-, aryl - Aryl-C ₁ -C ₄ alkyl or hetaryl-C ₁ -C ₄ alkyl group substituted amino group; an amino group substituted twice by C ₁ -C ₄ alkyl groups; or a heterocyclic five or six ring with one

Means nitrogen and oxygen atom; such as the ethoxy; n-propylamino, i-propylamino, iso-butylamino, t-butylamino, 2-hydroxypropylamino, cyclopropylamino, cyclopentylamino, cyclopropylmethylamino, cyclopentylmethylamino, Ethoxycarbonyl-methylamino, phenylamino, benzylamino, phenyl-ethylamino, 1-phenyl-2-propylamino group, where the phenyl parts can be substituted by methyl, methoxy or chlorine, or the thienylmethylamino, pyridylmethylamino, furylmethylamino or morpholino group,

R _{3 is} a hydrogen atom,

R4 represents a hydrogen atom, a triphosphate group or an acetyl group.

Possible salts of the compounds of the general formula I are, in particular, alkali, alkaline earth and ammonium salts of the phosphate groups. Lithium, sodium and potassium salts are preferred as alkali salts. Magnesium and calcium salts are particularly suitable as alkaline earth metal salts. According to the invention, ammonium salts are understood to be salts which contain the ammonium ion, which can be substituted up to four times by alkyl radicals with 1-4 carbon atoms and / or aralkyl radicals, preferably benzyl radicals. The substituents can be the same or different.

The compounds of the general formula I can contain basic groups, in particular amino groups, which can be converted into acid addition salts using suitable acids. Examples of suitable acids for this purpose are: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, tartaric acid, citric acid, lactic acid, maleic acid or methanesulfonic acid. The compounds of general formula I are new compounds. They can be prepared in analogy to known, related compounds (Robins, Hansske THL 25, 367, 1984 and the literature cited therein). For the preparation of the compounds of the general formula I, a process has proven to be particularly expedient in which a compound of the general formula II

in which R ₁ , R ₂ and R _{3 have} the meaning given, with a compound of the general formula III

in which X is halogen such as fluorine, chlorine, bromine or iodine, to a mixture of the isomers IV a, b and V a, b

in which R ₁ , R ₂ , R ₃ , R ₄ and X have the meaning given, and then the mixture of the isomers IV a, b and V a, b with a reducing agent such as the zinc / copper couple or similar reducing agents

reduced and from the crude product obtained after splitting off the protective group from the compounds IV b and V b with ammonia, the compounds of general formula I is obtained.

In addition to this method, further methods for dideoxygenation and simultaneous introduction of the double bond are described in the literature (cf.Jain et al. JOC 39, 30, 1974, Robins et al. JACS 98, 8204 and 8213, 1976, Adachi et al. JOC 44 , 1404, 1979, Mengel et al. THL 4203, 1977, Classon et al. Acta Chem. Scand. B 36, 251, 1982; Chu et al. JOC 54, 2217, 1989). Furthermore, compounds of the general formula I can be obtained from corresponding 2'-deoxyriboses by known processes (cf. Horwitz et al JACS 86, 1896, 1964, McCarthy et al. JACS 88, 1549, 1966, Samukov et al. Biorg. Khim. 9, 52, 1982) of monodeoxygenation with simultaneous introduction of the double bond. Another way of preparing the compounds of the general formula I is to react a 2 ', 3'-dideoxy-2', 3'-didehydroribose with a correspondingly substituted purine derivative as is known to a person skilled in the art from the literature (cf., for example, EP 0,286,028) are. Another method for producing analogous substances is described in US Pat. No. 3,817,982.

Compounds of the formula II are either already known from the literature (cf. EP-A-286,425) or can be prepared by known processes. A common method is, for example, the reaction of 6-chloro-substituted purine derivatives (Nucleic Acid Chemistry, Ed .: LB Tounsend, RS Tipson, Part II, p. 611, John Wiley and Sons, 1978 and the literature cited therein) Nucleophiles such as primary and secondary amines, alcohols or

Thiols.

For the manufacture of medicaments, the substances of the general formula I are mixed in a manner known per se with suitable pharmaceutical carriers, flavorings, flavors and colors and shaped, for example, as tablets or dragées or with the addition of appropriate auxiliaries in water or oil, such as, for. B. olive oil, suspended or dissolved. The new substances of general formula I according to the invention and their salts can be administered enterally or parenterally in liquid or solid form. Water is preferably used as the injection medium, which contains the additives customary for injection solutions, such as stabilizers, solubilizers or buffers. Such additives are e.g. B. tartrate and citrate buffers, ethanol, Complexing agents (such as ethylenediaminetetraacetic acid and its non-toxic salts) and high-molecular polymers (such as liquid polyethylene oxide) for viscosity regulation.

Solid carriers are e.g. Starch, lactose, mannitol, methyl cellulose, talc, highly disperse silicas, high molecular fatty acids (such as stearic acid), gelatin, agar agar, calcium phosphate, magnesium stearate, animal and vegetable fats and solid high molecular polymers (such as polyethylene glycols). Preparations suitable for oral administration can, if desired, contain flavorings and sweeteners.

The compounds according to the invention are usually applied in amounts of 0.1-100 mg, preferably 0.2-80 mg per day and per kg of body weight. It is preferred to distribute the daily dose over 2-5 applications, 1-2 tablets with an active ingredient content of 0.5-1000 mg being administered with each application. The tablets can also be delayed, which reduces the number of applications per day to 1-3. The active substance content of the retarded tablets can be 20 - 2000 mg. The active ingredient can also be given by injection one to eight times a day or by continuous infusion, with amounts of 5-4000 mg per day usually being sufficient.

In addition to the compounds mentioned in the examples, the following substances are particularly preferred:

1. 6-piperidino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

2. 6-chloro-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

3. 6-ethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

4. 6-ethylmethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

5. 6-iodo-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

6. 6-Cyclopropylmethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

7. 6-Isopropylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

8. 2-Amino-6-n-propoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

9. 6-ethylthio-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

10. 2-Amino-6-benzylthio-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

11. 6-Ethoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine 12. 6-Hydroxyethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

13. 6-Cyclopentylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

14. 2-Amino-6-methoxy-2 ', 3'-dideoxy-2 *, 3'-didehydro-9-β-D-ribofuranosylpurine

15. 6-n-Propoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

16. 6-n-Butoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

17. 6-Cyclopropylmethoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

18. 6-Cyclopentyloxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

19. 6-Cyclohexyloxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

20. 6-Cyclobutylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

21. 6-Diethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

22. 6-Pyrrolidino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

23. 2-Amino-6-morpholino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine 24. 6-gamma, gamma-dimethylallylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

25. 6- (2-Furylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

26. 6-Benzylmercapto-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

27. 6-phenylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

28. 2-Amino-6-ethoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

29. 2,6,8-triamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

30. 2-Amino-6-benzylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

31. 2-Amino-6-cyclopropylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

32. 2-Amino-6-methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

33. 2-Amino-6-n-propoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

34. 6-Benzylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

35. 6-isopropoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine 36. 6-Cyclohexylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

37. 6- (2-methyl) allylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

38. 6-Methyl-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

39. 6-Cyclopentylmethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-0-ß-D-riböfuranosylpurin

40. 6- (Cyclopenten-1-yl) methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

41. 6-Hexylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

42. 6-Neopentylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosyIpurin

43. 6- (2-Hydroxy-1-propyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

44. 6- (2,2-Dimethoxy-1-ethyl-) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-ribofuranosylpurine

45. 6-Ethoxycarbonylmethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

46. 6- (4-Chlorobenzyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

47. 6- (4-methoxybenzyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine 48. 6- (3-Methylbenzyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

49. 6- (4-Methylbenzyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

50. 6- (2-Furylmethyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

51. 6- (2-Thienylmethyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

52. 6- (2-pyridylmethyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

53. 6- (3-pyridylmethyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

54. 6- (4-pyridylmethyl) amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine

example 1

6-Propylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine a) 100 ml chloroform, 2.1 ml dist. Dimethylformamide and 5.5 ml (76 mmol) of thionyl chloride were placed under nitrogen and stirred for 15 minutes at room temperature. 10 g (25 mmol) of 2 ', 3', 5'-triacetylinosine were added and the clear solution was stirred under reflux for 5 hours. The mixture was poured into a solution of 250 ml of water and 6.25 g of sodium hydrogen carbonate, extracted several times with dichloromethane, the organic phase was neutralized again with 250 ml of sodium hydrogen carbonate solution, dried over sodium sulfate and then evaporated to dryness. 10.6 g of 6-chloro-9-β-D-ribofuranosylpurine are obtained as an oil. b) 4.1 g of the compound obtained under a) are stirred with 30 ml of isopropanol and 2.3 g (39 mmol) of n-propylamine for 3 days under reflux. The mixture was brought to dryness, the residue was dissolved in isopropanol and stirred with 10 ml of a 1 molar sodium methylate solution at reflux for one hour. The mixture was brought to dryness and purified on a silica gel column (mobile phase: dichloromethane / methanol 98: 2). 2.0 g (68%) of 6-propylamino-9-β-D-ribofuranosylpurine, mp. 165-167 ° C., are obtained. c) 2.0 g (6.47 mmol) of the compound obtained under b) were dissolved in 110 ml of absolute acetonitrile, 4 ml (26 mmol) of acetoxyisobutyryl bromide were added dropwise and

Stirred for 2 hours at room temperature. The mixture was neutralized with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phase was dried over sodium sulfate and then evaporated to dryness. 3.2 g are obtained which were further reacted without purification. d) 2 g of the crude product obtained under c) were dissolved in 32 ml of absolute dimethylformamide, an excess of zinc / copper pair was added and the mixture was stirred for one hour with the exclusion of moisture. The solid residues were suctioned off and the solvent was distilled off in a high vacuum. The residue was taken up in 140 ml of ammoniacal methanol and stirred at room temperature for 2 hours. The mixture was brought to dryness and purified on a silica gel column (mobile phase: dichloromethane / methanol 98: 2) and the desired fractions were stirred with ether after evaporation. 0.3 g (68%) of the title compound of mp 146-150 ° C. is obtained.

Example 2

The following end compounds are obtained analogously to Example 1 ad: a) 6- (2-methylphenylmethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 58% yield from the mp. 141-142 ° C. b) 6-Dimethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 78% yield, mp. 134-137 ° C. c) 6-Allylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 51% yield, mp. 138-140 ° C. d) 6-isobutylamino-2 ', 3-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 49% yield as a foam. e) 6-Morpholino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 71% yield, mp. 75-83 ° C (dec.). f) (L) -6- (1-phenyl-2-propylamino) -2 ', 3'-dideoxy-2', 3'-dideydro-9-ß-D-ribofuranosylpurine in 54% yield, mp. 68- 75 ° (dec.). g) 6-Cyclopropylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 47% yield, mp. 112-114 ° C. h) 6- (2-phenylethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 58% yield, mp. 116-117 ° C. i) 6-methylmercapto-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 57% yield, mp. 133-136 ° C. j) 6-phenylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß D-ribofuranosylpurine in 47% yield, mp. 123-125 ° C. k) 6-methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 64% yield, mp. 87-92 ° C. l) 6-ethoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine in 45% of mp 128-131 ° C. m) 6-gamma, gamma-dimethylallylamino-2 ', 3'-dideoxy-

2 ', 3'-didehydro-9-ß-D-ribofuranosylpurine in 48% of mp. 105-109 ° C. Example 3

6-propylamino-2 ', 3'-dideoxy-2', 3'-didehvdro-9-ß

D-ribofuranosylpurine 5'-triphosphate x 3 mol NEt ₃

55.1 mg (0.2 mmol) of 6-propylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine (Ex. 1) were in absolute. Suspended toluene and brought to dryness in a high vacuum at room temperature (2x1ml). The residue was dissolved in 2 ml of trimethyl phosphoric acid at 25 ° C., cooled in an ice bath, 85 mg (0.4 mmol) of proton sponge (1,8-bis-dimethylamino-naphthalene) were added,

0.027ml (0.15mmol) of phosphorus oxychloride was added dropwise and 0.04ml absolute after 15 minutes. DMF added. The mixture was stirred in an ice bath for a further 15 minutes and then added dropwise to a solution of 0.5 mmol bis-tributylammonium pyrophosphate, 2 ml DMF, 2 ml pyridine and 0.2 ml tributylamine while cooling with ice. After 5 minutes the

Reactions 2 ml of a 0.2 molar, aqueous triethylammonium hydrogen carbonate solution are added, the mixture is diluted with water after 30 minutes, applied to a Sephadex DEAE column and with a 0.1-0.5 molar, linear gradient of triethylammonium hydrogen carbonate eluted. The desired fractions were combined and 68 mg was obtained after two lyophilization

(41.7%) of the title compound as the tris-triethylaitimonium salt.

3 ¹ p-NMR (D ₂ O / H ₂ O + ethylenediaminetetraacetic acid): δ = -7.70 (d, P-α and Pτ), -20.16 (t, P-ß). Example 4

The following end compounds are obtained analogously to Example 3: a) 6- (2-methylphenylmethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine-5'-triphosphate x 3 mol NEt ₃

³¹ P NMR: δ = -8.51 (d, P-α and P-τ), -21.04 (t, P-ß). b) 6-Dimethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine-5'-triphosphate x 3 mol NEt ₃ , 3 ¹ P-NMR: δ = -7.60 (d, P-α), -7.79 (d, P-τ), -20.14 (t, P-ß). c) 6-Allylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine-5'-triphosphate x 3 mol NEt ₃ , 3 ¹ P-NMR: δ = -8.50 (d, P-α), -8.74 (d, P-τ), -21.03 (t, P-ß). d) 6-isobutylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine-5'-triphosphate x 3 mol NEt ₃ , 3 ¹ P-NMR: δ = -8.51 (d, P-α), -8.58 (d, P-τ), -21.08 (t, P-ß) e) 6-morphαlino-2 ', 3'-dideoxy-2', 3'-didehydro-9 -ß-D-ribofuranosylpurin-5'-triphosphate x 3 mol NEt ₃ , 3 ¹ P-NMR: δ = -8.62 (d, P-α), -8.73 (d, P-τ), -21.08 (t, P-β) f) (L) -6- (1-phenyl-2-propylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-β-D-ribofuranosylpurine-5'-triphosphate x 3 mol NEt ₃ ,

³¹ P-NMR: δ = -8.25 (d, P-α), -8.53 (d, P-τ), -20.98 (t, P-ß) g) 6- (2-phenylethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine-5'-triphosphate x

3 mol NEt ₃ ,

3 ¹ P-NMR: δ = -8.53 (d, P-α and P-τ), -20.97 (t, P-ß) h) 6-methylmercapto-2 ', 3'-dideoxy-2', 3 '-didehydro-9-ß-D-ribofuranosylpurine-5'-triphosphate x 3 mol NE + ₃ , 3 ¹ p-NMR: δ = -8.53 (d, P-α), -8.58 (d, P-τ), - 21.14 (t, P-ß) i) 6-methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine-5'-triphosphate x 3 mol NEt ₃ , 3 ¹ P-NMR: δ = -7.61 (d, P-α), -7.80 (d, P-τ), -20.12 (t, P-ß)

Example 5

2-Amino-6-methylamino-2 ', 3'-dideoxy-2', 3'-didehvdro-9-ß-D-ribofuranosylpurine a) 3.5g (11.8mmol) 2-amino-6-methylamino-9 -ß-D-ribofuranosylpurin were absolute in 70. DMF dissolved and 1.93 g (28.3 mmol) imidazole added. 2.14 g (14.2 mmol) was then tert while stirring. Butyldimethysilyl chloride was added dropwise and stirring was continued for 20 hours. The solvent was distilled off under high vacuum and the residue was purified by column chromatography on silica gel (mobile solvent: dichloromethane / methanol, 98: 2). 3.18 g of 2-amino-6-methylamino-5'-O- (tert-butyl-dimethylsilyl) -9-β-D-ribofuranosylpurine are obtained as amorphous

Solid. b) 0.44 g (1.07 mmol) of the compound obtained under a) were dissolved in 3 ml of DMSO, 0.27 g (3.58 mmol) of CS ₂ and 0.46 ml of 5 molar NaOH solution were added after 20 Minutes 0.34 g (2.36 mmol) of methyl iodide was added dropwise and stirring was continued at 25 ° C. for 2 hours. The solvent was distilled off under high vacuum and the residue was chromatographed on silica gel (eluent: ethyl acetate). The fractions of the main product were evaporated and crystallized from ether / isohexane. 0.3 g of 2-amino-6-methylamino-5'-O- (tert-butyldimethylsilyl) -2 ', 3'-bis-0- (methylthio) thiocarbonyl-9-ß-D-ribofuranosylpurine is obtained. c) 0.3 g (0.5 mmol) of the compound obtained under b) were heated to reflux temperature in 24 ml of toluene and a solution of 0.58 g (2.0 mmol) of tri-n-butyltin hydride and 27 mg (0.16 mmol) of azoisobutyronitrile in 25 ml of toluene was added dropwise . After 1 hour the evaporated residue was purified on silica gel (eluent: ethyl acetate / methanol, 99: 1). 0.1 g of 2-amino-6-methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-5'-O- (tert-butyldimethylsilyl) -9-β-D-ribofuranosylpurine of mp. 97-99 ° C. d) 0.1 g (0.26 mmol) of the compound obtained under c) are absolute in 5 ml. THF mixed with 0.08 ml of a 1 molar solution of tetrabutylammonium fluoride in THF. After 5 hours at 25 ° C., the mixture is brought to dryness, taken up in CH ₂ Cl ₂ , washed with water and dried. After chromatography on silica gel (mobile phase: ethyl acetate), 60 mg of the title compound of mp. 108-110 ° C. are obtained. Example 6

The following end compounds are obtained analogously to Example 5 ad: a) 2-hydroxy-6-methylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp b) 2- Amino-6-ethoxy-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp. C) 6- (2-thienylmethylamino) -2 ', 3'-dideoxy- 2 ', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp. 150-152 ° C d) 6- (2-pyridylmethylamino) -2', 3'-dideoxy-2 ', 3'-didehydro-9 -ß-D-ribofuranosylpurine, mp. 154-156 ° C e) 6- (4-methylphenylmethylamino) -2 ', 3'-dideoxy-2'3'-didehydro-9-ß-D-ribofuranosylpurine, mp. 133 -135 ° C f) 6-isopropylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp. 132-133 ° C g) 6-cyclopentylmethylamino-2 ', 3'-dideoxy-2 ', 3'-didehydro-9-ß-ribofuranosylpurine, mp. 131-133 ° C. h) 6-Phenylmethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, m.p. 127-128 ° C. i) 6- (4-methoxyphenylmethylamino) -2 ', 3'-dideoxy-2'3'-didehydro-9-β-D-ribofuranosylpurine, m.p. 127-129 ° C. j) 6-tert-Butylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp. 184-185 ° C. k) 6-Ethoxycarbonylmethylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, m.p. 118-120 ° C. l) 6- (2-hydroxypropylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, foam. m) 6- (4-chlorophenylmethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp. 155-157 ° C. n) 6- (3-Methylphenylmethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp. 102-105 ° C. o) 6- (2-furylmethylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine, mp 158-159 ° C.

Example 7

5'-acetyl-6- (2-methylphenylmethylamino) -2 ', 3'-dideoxy-2', 3'-didehvdro-9-β-D-ribofuranosylpurine

250 mg (0.75 mmol) of the compound obtained in Example 2a were mixed with 5 mg of dimethylaminopyridine and 113 mg (1.11 mmol) of acetic anhydride in 15 ml of dichloromethane and stirred at 25 ° C. for 4 hours. The solvent was then distilled off and the residue was chromatographed on silica gel 60 (mobile phase: CH ₂ Cl ₂ / CH ₃ OH, 99: 1). 200 mg of the title compound of mp 125 ° C. are obtained.

Claims

1. Purine nucleosides and nucleotides of the formula I

in the

R _{1 represents} a hydrogen atom or an amino group,

R _{2 is} a halogen atom; a C ₁ -C ₆ alkyl; C ₂ -C ₆ alkenyl;

C ₁ -C ₆ alkoxy-; C ₃ -C ₆ cycloalkyl-C ₁ -C ₆ alkoxy-; C ₃ -C ₈ cycloalkyloxy-; C ₃ -C ₆ cycloalkylthio-; C ₁ -C ₆ alkylthio group; or R _{2 represents} an amino group R ₅ R ₆ N-, in which one of the radicals R ₅ or R _{6 can be} a hydrogen atom, and otherwise R ₅ and R _{6 can be the} same or different and independently of one another a C ₁ -C ₆ - Alkyl, C ₂ -C ₆ alkenyl, C ₁ -C ₆ alkoxy, hydroxyC ₁ -C ₆ alkyl, C ₃ -C ₈ cycloalkyl, C ₃ -C ₈ cycloalkyl-C ₁ -C ₆ -alkyl, C ₃ - C ₈ -cycloalkenyl-C ₁ -C ₆ -alkyl-, C ₁ -C ₆ -alkoxy-C ₁ -C ₆ -alkyl-, di-C ₁ -C ₆ -alkoxy- C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxycarbonyl-C ₁ -C ₆ alkyl, aryl, aryl-C ₁ -C ₆ alkyl or hetaryl-C ₁ -C ₆ alkyl group ; or R ₂ an aryl, Ar-C ₁ -C ₆ alkyl, aryloxy, Ar-C ₁ -C ₆ alkyloxy, arylthio, Ar-C ₁ -C ₆ alkylthio or

Means hetarylthio group; the "aryl" and "hetaryl" parts in all the aforementioned cases of the aryl- or hetaryl-bearing groups one or more times by hydroxy, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy , Trifluoromethyl, amino or halogen groups may be substituted; or R _{2 represents} a saturated, unsaturated or aromatic heterocyclic ring with an oxygen atom and / or a sulfur atom and / or one or two nitrogen atoms and 3-7 carbon atoms, this ring being represented by one or more hydroxy, C ₁ -C ₆ alkyl -, Halogen or C ₃ -C ₆ - cycloalkylthio radicals can be substituted;

R _{3 represents} hydrogen or the amino group and

R _{4 is} hydrogen or a C ₁ -C ₆ alkylcarbonyl, or

means a mono-, di- or triphosphate group, their optically active forms, tautomers or physiologically tolerable salts of inorganic and organic acids and bases, with the exception of the compounds 6- methylamino-2 ', 3'-dideoxy-2', 3'-didehydro -9-ß-ribo-furanosyl-purine, 6-dimethyl-amino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-ribo-furanosyl-purine, 6-methylthio-2 ', 3'- dideoxy-2 ', 3'-didehydro-9-ß-ribofuranosyl-purine.

2. Purine nucleosides and nucleotides of the formula I according to

Claim 1, in the

R ₂ halogen; C ₁ -C ₆ alkoxy which may be substituted by C ₃ -C ₆ cycloalkyl; C ₃ -C ₈ cycloalkyloxy;

Aryloxy, aralkyl or aralkyloxy, the aryl radical of which is substituted by hydroxy, C ₁ -C ₆ alkyl or halogen can be; C ₃ -C ₆ cycloalkylthio; C ₁ -C ₆ alkylthio; Arylthio or aralkylthio, the aryl radical of which can be substituted by hydroxy, C ₁ -C ₆ alkyl or halogen, or R _{2 is} a saturated, unsaturated or aromatic heterocyclic ring having an oxygen atom and / or a sulfur atom and / or one or two nitrogen atoms. atoms and C ₃ -C ₇ carbon atoms and those in the ring by one or more hydroxy, C ₁ -C ₆ alkyl, halogen, C ₃ -C ₆ cycloalkylthio or aralkylthio radicals, which are optionally in the aryl radical hydroxy, C ₁ -C ₆ alkyl or

Halogen, may be substituted, means, or R _{2 is} an imidazolylthio group in which the imidazole residue with C ₁ -C ₃ alkyl and / or C-substituted with nitro means, or R _{2 is} an amino group which is mono- or is disubstituted by C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, hydroxy-C ₁ -C ₆ alkyl and / or C ₃ -C ₆ cycloalkyl; Aryl or aralkyl, the aryl radical of which may be substituted by hydroxy, C ₁ -C ₆ alkyl or halogen, or allyl, which may be substituted by one or more C ₁ -C ₆ alkyl or C ₁ -C ₆ alkoxy groups.

3. Purine nucleosides and nucleotides of the formula I according to

one of claims 1 or 2, characterized in that

R _{2 is} a C ₁ -C ₄ alkoxy, C ₁ -C ₄ alkylthio, simply by a C ₂ -C ₆ alkyl, C ₂ -C ₆ alkenyl, hydroxy C ₁ -C ₄ - alkyl-, C ₃ -C ₆ -cycloalkyl-, C ₃ -C ₆ -cycloalkyl-C ₁ -C ₄ -alkyl-, C ₁ -C ₄ -alkoxy-carbonyl-C ₁ -C ₄ -alkyl-, aryl - Aryl- C ₁ -C ₄ alkyl or hetaryl-C ₁ -C ₄ alkyl group substituted amino group; an amino group substituted twice by C ₂ -C ₄ alkyl groups; or a heterocyclic five or six ring having a nitrogen and oxygen atom.

4. Purine nucleosides and nucleotides according to any one of claims 1-3, wherein

R _{2 is} an ethoxy; n-propylamino, i-propylamino, i-butylamino, t-butylamino, 2-hydroxypropylamino, cyclopropylamino, cyclopentylamino, cyclopropylmethylamino, cyclopentylmethylamino, ethoxycarbonylmethylamino, phenylamino, benzyl -amino, phenyl-ethylamino, 1-phenyl-2-propylamino group, where the phenyl parts can be substituted by methyl, methoxy or chlorine, or the thienylmethylamino, pyridylmethylamino, furylmethylamino or morpholino group.

5. Purine nucleosides and nucleotides according to any one of claims 1-4, wherein

_{R3 represents} a hydrogen atom.

6. Purine nucleosides and nucleotides according to any one of claims 1-5, wherein

R _{4 represents} a hydrogen atom, a triphosphate or acetyl group.

7. The compounds according to claim 1 or 2:

6-Cyclopropylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

6- (2-Methylphenyl-methylamino) -2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine 6-allylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

6-isobutylamino-2 ', 3'-dideoxy-2', 3'-didehydro-9-ß-D-ribofuranosylpurine

8. A process for the preparation of compounds of formula I according to any one of claims 1-7, characterized in that a compound of formula II

in which X is halogen such as fluorine, chlorine, bromine or iodine, to a mixture of the isomers IV a, b and V a, b t

in which R ₁ , R2, R ₃ , R ₄ and X have the meaning given, and then the mixture of

Isomers IV a, b and V a, b with a reducing agent such as e.g. the zinc / copper pair or the like

Reduced reducing agents and from the crude product obtained after splitting off the protective group from the compounds IV b and V b with ammonia, the compounds of the general formula I, and, if desired, the compounds obtained are converted into physiologically tolerable salts in the customary manner.

9. Medicament containing at least one compound

according to one of claims 1 to 7 in addition to conventional

Carriers and auxiliaries.

10. Use of compounds according to any one of claims 1-7 for the manufacture of medicaments with antiviral activity.