CS277006B6 - Process for preparing antiviral substances - Google Patents
Process for preparing antiviral substances Download PDFInfo
- Publication number
- CS277006B6 CS277006B6 CS883635A CS363588A CS277006B6 CS 277006 B6 CS277006 B6 CS 277006B6 CS 883635 A CS883635 A CS 883635A CS 363588 A CS363588 A CS 363588A CS 277006 B6 CS277006 B6 CS 277006B6
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- purine
- arabinofuranosyl
- methoxy
- compound
- formula
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 239000000126 substance Substances 0.000 title description 17
- 230000000840 anti-viral effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- -1 purine arabinosides Chemical class 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 27
- 150000002148 esters Chemical class 0.000 claims abstract description 26
- 241000701085 Human alphaherpesvirus 3 Species 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 238000011321 prophylaxis Methods 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 229910052757 nitrogen Inorganic materials 0.000 claims description 72
- 239000004480 active ingredient Substances 0.000 claims description 55
- 239000000463 material Substances 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 208000015181 infectious disease Diseases 0.000 claims description 14
- 241000701022 Cytomegalovirus Species 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 208000036142 Viral infection Diseases 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 230000009385 viral infection Effects 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
- 150000005840 aryl radicals Chemical class 0.000 claims description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
- 150000005690 diesters Chemical class 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 150000005691 triesters Chemical class 0.000 claims description 3
- WVGPGNPCZPYCLK-QRKAXHLRSA-N (2r,3s,4s,5r)-2-[6-(dimethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N(C)C)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O WVGPGNPCZPYCLK-QRKAXHLRSA-N 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- IRZDOONJRAFUQI-LJGDNWOOSA-N [(2r,3s,4s,5r)-3,4-dihydroxy-5-(6-methoxypurin-9-yl)oxolan-2-yl]methyl 4-methylbenzoate Chemical compound C([C@H]1O[C@H]([C@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)OC)OC(=O)C1=CC=C(C)C=C1 IRZDOONJRAFUQI-LJGDNWOOSA-N 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 claims description 2
- 150000003212 purines Chemical group 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- VPBXAOGLYOZWSD-UHFFFAOYSA-N CCNC1(C(CCCN1N(C)C)OC)NC Chemical compound CCNC1(C(CCCN1N(C)C)OC)NC VPBXAOGLYOZWSD-UHFFFAOYSA-N 0.000 claims 1
- XBNIJOKVGOETFF-MBMVNNNZSA-N [(2r,3s,4s,5r)-3,4-dihydroxy-5-(6-methoxypurin-9-yl)oxolan-2-yl]methyl 4-aminobenzoate Chemical compound C([C@H]1O[C@H]([C@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)OC)OC(=O)C1=CC=C(N)C=C1 XBNIJOKVGOETFF-MBMVNNNZSA-N 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 abstract description 3
- 208000005181 Varicella Zoster Virus Infection Diseases 0.000 abstract 1
- 208000010531 varicella zoster infection Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 132
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 124
- 239000000047 product Substances 0.000 description 105
- 239000000203 mixture Substances 0.000 description 102
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 92
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- 229910052799 carbon Inorganic materials 0.000 description 69
- 239000000243 solution Substances 0.000 description 58
- 239000000741 silica gel Substances 0.000 description 57
- 229910002027 silica gel Inorganic materials 0.000 description 57
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 46
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 45
- 238000005481 NMR spectroscopy Methods 0.000 description 42
- 238000004949 mass spectrometry Methods 0.000 description 42
- 238000003818 flash chromatography Methods 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 36
- 239000002904 solvent Substances 0.000 description 36
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000007792 addition Methods 0.000 description 23
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- 239000003826 tablet Substances 0.000 description 22
- UQQHOWKTDKKTHO-ICQCTTRCSA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolane-3,4-diol Chemical compound C1=NC=2C(OC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O UQQHOWKTDKKTHO-ICQCTTRCSA-N 0.000 description 21
- 239000011347 resin Substances 0.000 description 20
- 229920005989 resin Polymers 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 239000002775 capsule Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 239000000377 silicon dioxide Substances 0.000 description 16
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
- 229910052786 argon Inorganic materials 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- 239000004615 ingredient Substances 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 description 11
- 102000030764 Purine-nucleoside phosphorylase Human genes 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 102000006405 Uridine phosphorylase Human genes 0.000 description 10
- 108010019092 Uridine phosphorylase Proteins 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- DRTQHJPVMGBUCF-CCXZUQQUSA-N arauridine Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-CCXZUQQUSA-N 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 239000008101 lactose Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 8
- 229910000160 potassium phosphate Inorganic materials 0.000 description 8
- 235000011009 potassium phosphates Nutrition 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
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- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
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- 235000019197 fats Nutrition 0.000 description 6
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 5
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- 238000001704 evaporation Methods 0.000 description 5
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- 239000001226 triphosphate Substances 0.000 description 5
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
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- 125000005843 halogen group Chemical group 0.000 description 4
- DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 4
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878712745A GB8712745D0 (en) | 1987-05-30 | 1987-05-30 | Antiviral compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS8803635A2 CS8803635A2 (en) | 1990-09-12 |
| CS277006B6 true CS277006B6 (en) | 1992-11-18 |
Family
ID=10618179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS883635A CS277006B6 (en) | 1987-05-30 | 1988-05-27 | Process for preparing antiviral substances |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US5424295A (es) |
| EP (1) | EP0294114B1 (es) |
| JP (1) | JP2667873B2 (es) |
| KR (1) | KR970009474B1 (es) |
| CN (1) | CN1020107C (es) |
| AT (1) | ATE142636T1 (es) |
| AU (1) | AU622403B2 (es) |
| CA (1) | CA1330990C (es) |
| CS (1) | CS277006B6 (es) |
| CY (2) | CY2001A (es) |
| DD (2) | DD293962A5 (es) |
| DE (2) | DE122008000003I2 (es) |
| DK (1) | DK171670B1 (es) |
| ES (1) | ES2091750T3 (es) |
| FI (1) | FI89805C (es) |
| GB (1) | GB8712745D0 (es) |
| GR (1) | GR3021257T3 (es) |
| HK (1) | HK78497A (es) |
| HU (2) | HU205001B (es) |
| IL (1) | IL86531A (es) |
| LU (1) | LU91370I2 (es) |
| MC (1) | MC1935A1 (es) |
| MY (1) | MY103567A (es) |
| NL (1) | NL300302I2 (es) |
| NO (2) | NO172543C (es) |
| NZ (1) | NZ224813A (es) |
| PH (1) | PH27292A (es) |
| PL (1) | PL157684B1 (es) |
| PT (1) | PT87592B (es) |
| SA (1) | SA99200688A (es) |
| ZA (2) | ZA883829B (es) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8712745D0 (en) * | 1987-05-30 | 1987-07-01 | Wellcome Found | Antiviral compounds |
| US7307166B1 (en) * | 1987-10-28 | 2007-12-11 | Wellstat Therapeutics Corporation | Oxpurine nucleosides and their congeners, and acyl, derivatives thereof, for improvement of hematopoiesis |
| DD293498A5 (de) * | 1989-07-20 | 1991-09-05 | Zi Fuer Molekularbiologie Der Adw,De | Verfahren zur herstellung eines mittels fuer die behandlung oder prophylaxe von hepatits-infektionen bei mensch und tier |
| GB8919607D0 (en) | 1989-08-30 | 1989-10-11 | Wellcome Found | Novel entities for cancer therapy |
| US6337209B1 (en) | 1992-02-26 | 2002-01-08 | Glaxo Wellcome Inc. | Molecular constructs containing a carcinoembryonic antigen regulatory sequence |
| KR910007655A (ko) * | 1989-10-03 | 1991-05-30 | 엠. 피. 잭슨 | 치료용 뉴클레오시드 |
| US5206351A (en) * | 1990-06-15 | 1993-04-27 | Ash Stevens, Inc. | Process for the preparation of 2-amino (2,3,5-tri-o-benzyl-beta-d-arabinofuranosyl)adenine |
| GB9015914D0 (en) * | 1990-07-19 | 1990-09-05 | Wellcome Found | Heterocyclic compounds |
| US5283331A (en) * | 1990-12-20 | 1994-02-01 | Nippon Kayaku Kabushiki Kaisha | 2-halogeno-oxetanocin A and phosphoric ester thereof |
| GB9104165D0 (en) * | 1991-02-27 | 1991-04-17 | Wellcome Found | Novel entities for hiv therapy |
| US5961987A (en) * | 1996-10-31 | 1999-10-05 | University Of Iowa Research Foundation | Ocular protein stimulants |
| JP3619017B2 (ja) | 1998-06-24 | 2005-02-09 | 日本臓器製薬株式会社 | 新規アラビノシルアデニン誘導体 |
| US6653318B1 (en) | 1999-07-21 | 2003-11-25 | Yale University | 5-(E)-Bromovinyl uracil analogues and related pyrimidine nucleosides as anti-viral agents and methods of use |
| AU2001238516B2 (en) * | 2000-02-18 | 2005-08-04 | Southern Research Institute | Methods for synthesizing 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H- purin-6-amine |
| US6753322B2 (en) * | 2000-06-06 | 2004-06-22 | Pfizer Inc | 2-aminocarbonyl-9H-purine derivatives |
| JP3421330B2 (ja) * | 2000-11-02 | 2003-06-30 | 持田製薬株式会社 | ビダラビン注射用乾燥製剤 |
| JP4493337B2 (ja) * | 2001-11-27 | 2010-06-30 | アナディス ファーマシューティカルズ インク | ３−β−Ｄ−リボフラノシルチアゾロ［４，５−ｄ］ピリミジンヌクレオシド及びその使用 |
| US7321033B2 (en) * | 2001-11-27 | 2008-01-22 | Anadys Pharmaceuticals, Inc. | 3-B-D-ribofuranosylthiazolo [4,5-d] pyrimidine nucleosides and uses thereof |
| WO2004028481A2 (en) * | 2002-09-30 | 2004-04-08 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis c virus infection |
| PT1824482E (pt) * | 2004-12-17 | 2014-05-13 | Anadys Pharmaceuticals Inc | Compostos 3h-oxazolo e 3h-tiazolo[4,5-d]pirimidin-2-ona 3,5- -di-substituídos e 3,5,7-tri-substituídos e seus pró- -fármacos |
| US20060178512A1 (en) * | 2005-02-04 | 2006-08-10 | Cheruthur Govindan | Method for preparing amino acid esters of nucleoside analogues |
| SG152296A1 (en) | 2005-11-21 | 2009-05-29 | Anadys Pharmaceuticals Inc | Novel process for the preparation of 5-amino-3h-thiazolo[4,5-d]pyrimidin-2- one |
| CA2655904C (en) * | 2006-06-22 | 2014-11-18 | Anadys Pharmaceuticals, Inc. | Prodrugs of 5-amino-3-(3'-deoxy-.beta.-d-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2,7-dione |
| JP5225991B2 (ja) | 2006-07-18 | 2013-07-03 | アナディス ファーマシューティカルズ インク | チアゾロ［４，５−ｄ］ピリミジンのカーボネート及びカルバメートプロドラッグ |
| CN101092441A (zh) * | 2007-07-17 | 2007-12-26 | 北京本草天源药物研究院 | 一种奈拉滨的合成方法 |
| US7846912B2 (en) * | 2007-09-13 | 2010-12-07 | Protia, Llc | Deuterium-enriched nelarabine |
| CN101768197A (zh) * | 2008-12-29 | 2010-07-07 | 北京德众万全药物技术开发有限公司 | 一种奈拉滨的制备方法 |
| CN103665076B (zh) * | 2012-08-30 | 2018-01-09 | 上海阳帆医药科技有限公司 | 奈拉滨的制备方法 |
| CN104892709B (zh) * | 2015-06-04 | 2018-01-19 | 新乡学院 | 一种合成奈拉滨的方法 |
| WO2018133835A1 (en) * | 2017-01-20 | 2018-07-26 | National Institute Of Biological Sciences, Beijing | Nucleoside analogue regulating mammalian circadian rhythm |
| WO2022258014A1 (zh) * | 2021-06-09 | 2022-12-15 | 正大天晴药业集团股份有限公司 | 用于制备奈拉滨的重组基因工程菌及其应用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE759011A (fr) * | 1969-11-17 | 1971-05-17 | Wellcome Found | Aminopurines |
| US3758684A (en) * | 1971-09-07 | 1973-09-11 | Burroughs Wellcome Co | Treating dna virus infections with amino purine derivatives |
| US4055717A (en) * | 1976-05-17 | 1977-10-25 | Parke, Davis & Company | 9-(3-O-Acyl-β-D-arabinofuranosyl)adenine compounds, 9-(2,3-di-O-acyl-β-D-arabinofuranosyl)-adenine compounds, and method for their production |
| US4055718A (en) * | 1976-05-17 | 1977-10-25 | Parke, Davis & Company | 9-(2-O-Acyl-β-D-arabinofuranosyl)-adenine compounds and method for their production |
| US4048432A (en) * | 1976-05-17 | 1977-09-13 | Parke, Davis & Company | 9-(3,5-Di-O-acyl-β-D-arabinofuranosyl)adenine compounds and method for their production |
| JPS6053941B2 (ja) * | 1977-08-10 | 1985-11-28 | 日本電気株式会社 | バイアスライト駆動方式 |
| JPS5515716A (en) * | 1978-07-18 | 1980-02-04 | Ajinomoto Co Inc | Production of purine arabinoside |
| US4371613A (en) * | 1977-08-10 | 1983-02-01 | Ajinomoto Company Incorporated | Method for producing purine arabinosides |
| GB1573777A (en) * | 1977-11-03 | 1980-08-28 | Wellcome Found | 9-d-arabinonucleosides and an enzymatic process for their preparation |
| US4495180A (en) * | 1982-06-21 | 1985-01-22 | Merck & Co., Inc. | Prodrugs of Ara-A an antiviral agent |
| JPS58225097A (ja) * | 1982-06-23 | 1983-12-27 | Yamasa Shoyu Co Ltd | ヌクレオシド５′−アルキルもしくはアルケニルりん酸 |
| EP0199451B1 (en) * | 1985-03-16 | 1996-03-06 | The Wellcome Foundation Limited | Therapeutic nucleosides |
| GB8712745D0 (en) * | 1987-05-30 | 1987-07-01 | Wellcome Found | Antiviral compounds |
-
1987
- 1987-05-30 GB GB878712745A patent/GB8712745D0/en active Pending
-
1988
- 1988-05-27 AT AT88304813T patent/ATE142636T1/de active
- 1988-05-27 DD DD88340139A patent/DD293962A5/de not_active IP Right Cessation
- 1988-05-27 NZ NZ224813A patent/NZ224813A/en unknown
- 1988-05-27 IL IL86531A patent/IL86531A/xx active Protection Beyond IP Right Term
- 1988-05-27 CA CA000567966A patent/CA1330990C/en not_active Expired - Lifetime
- 1988-05-27 EP EP88304813A patent/EP0294114B1/en not_active Expired - Lifetime
- 1988-05-27 JP JP63128562A patent/JP2667873B2/ja not_active Expired - Lifetime
- 1988-05-27 CN CN88103820A patent/CN1020107C/zh not_active Expired - Lifetime
- 1988-05-27 CS CS883635A patent/CS277006B6/cs not_active IP Right Cessation
- 1988-05-27 ES ES88304813T patent/ES2091750T3/es not_active Expired - Lifetime
- 1988-05-27 HU HU895829A patent/HU205001B/hu unknown
- 1988-05-27 HU HU882706A patent/HU199870B/hu active Protection Beyond IP Right Term
- 1988-05-27 MY MYPI88000569A patent/MY103567A/en unknown
- 1988-05-27 DE DE122008000003C patent/DE122008000003I2/de active Active
- 1988-05-27 DE DE3855522T patent/DE3855522T2/de not_active Expired - Lifetime
- 1988-05-27 AU AU16718/88A patent/AU622403B2/en not_active Expired
- 1988-05-27 PL PL1988272729A patent/PL157684B1/pl unknown
- 1988-05-27 PT PT87592A patent/PT87592B/pt not_active IP Right Cessation
- 1988-05-27 KR KR1019880006295A patent/KR970009474B1/ko not_active IP Right Cessation
- 1988-05-27 FI FI882511A patent/FI89805C/fi not_active IP Right Cessation
- 1988-05-27 DK DK289788A patent/DK171670B1/da not_active IP Right Cessation
- 1988-05-27 NO NO882357A patent/NO172543C/no not_active IP Right Cessation
- 1988-05-27 MC MC881981A patent/MC1935A1/xx unknown
- 1988-05-27 ZA ZA883829A patent/ZA883829B/xx unknown
- 1988-05-27 DD DD88316143A patent/DD282694A5/de not_active IP Right Cessation
-
1989
- 1989-09-01 PH PH39191A patent/PH27292A/en unknown
- 1989-10-05 ZA ZA897598A patent/ZA897598B/xx unknown
-
1993
- 1993-08-23 US US08/110,487 patent/US5424295A/en not_active Expired - Lifetime
-
1995
- 1995-03-14 US US08/403,363 patent/US5539098A/en not_active Expired - Lifetime
-
1996
- 1996-10-03 GR GR960402608T patent/GR3021257T3/el unknown
-
1997
- 1997-06-12 HK HK78497A patent/HK78497A/xx not_active IP Right Cessation
- 1997-12-05 CY CY200197A patent/CY2001A/xx unknown
-
1999
- 1999-10-18 SA SA99200688A patent/SA99200688A/ar unknown
-
2007
- 2007-10-10 LU LU91370C patent/LU91370I2/fr unknown
- 2007-11-02 NL NL300302C patent/NL300302I2/nl unknown
- 2007-12-21 NO NO2007016C patent/NO2007016I2/no unknown
-
2008
- 2008-01-25 CY CY200800001C patent/CY2008001I1/el unknown
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Legal Events
| Date | Code | Title | Description |
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| IF00 | In force as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20080527 |