CN88100826A - 核苷酸类似物的生产及其使用 - Google Patents
核苷酸类似物的生产及其使用 Download PDFInfo
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- CN88100826A CN88100826A CN198888100826A CN88100826A CN88100826A CN 88100826 A CN88100826 A CN 88100826A CN 198888100826 A CN198888100826 A CN 198888100826A CN 88100826 A CN88100826 A CN 88100826A CN 88100826 A CN88100826 A CN 88100826A
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- 125000003729 nucleotide group Chemical group 0.000 title description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 59
- 239000000126 substance Substances 0.000 claims abstract description 53
- 239000001257 hydrogen Substances 0.000 claims abstract description 50
- -1 5-amino-4-carbamoyl-imidazol-1-yl Chemical group 0.000 claims abstract description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 25
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 21
- 125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 claims abstract description 9
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 122
- 239000000203 mixture Substances 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 27
- 230000026731 phosphorylation Effects 0.000 claims description 24
- 238000006366 phosphorylation reaction Methods 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 239000003443 antiviral agent Substances 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- 239000005457 ice water Substances 0.000 claims description 6
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- 238000007363 ring formation reaction Methods 0.000 claims description 4
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical group NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 3
- 108020004707 nucleic acids Proteins 0.000 claims description 3
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- 125000001183 hydrocarbyl group Chemical group 0.000 claims 4
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- 125000003738 guanin-9-yl group Chemical group O=C1N([H])C(N([H])[H])=NC2=C1N=C([H])N2[*] 0.000 claims 3
- 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 abstract description 17
- 239000000243 solution Substances 0.000 description 80
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- 125000006239 protecting group Chemical group 0.000 description 13
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
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- 239000007864 aqueous solution Substances 0.000 description 6
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- 238000001914 filtration Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 235000011007 phosphoric acid Nutrition 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 238000000862 absorption spectrum Methods 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
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- 239000000725 suspension Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical class C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- KIDOTSCXAILVGR-APOSLCTFSA-N 2-amino-9-[(1r,2s,3r,4r)-2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1C[C@H](CO)[C@@H](O)[C@H]1O KIDOTSCXAILVGR-APOSLCTFSA-N 0.000 description 3
- QRZMXADUXZADTF-UHFFFAOYSA-N 4-aminoimidazole Chemical compound NC1=CNC=N1 QRZMXADUXZADTF-UHFFFAOYSA-N 0.000 description 3
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 3
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- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 3
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- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
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- OXMKRYBQXKJXBT-UHFFFAOYSA-N phosphono dihydrogen phosphate hydrochloride Chemical compound OP(O)(=O)OP(=O)(O)O.Cl OXMKRYBQXKJXBT-UHFFFAOYSA-N 0.000 description 1
- WRMXOVHLRUVREB-UHFFFAOYSA-N phosphono phosphate;tributylazanium Chemical compound OP(O)(=O)OP([O-])([O-])=O.CCCC[NH+](CCCC)CCCC.CCCC[NH+](CCCC)CCCC WRMXOVHLRUVREB-UHFFFAOYSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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- CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VKFFEYLSKIYTSJ-UHFFFAOYSA-N tetraazanium;phosphonato phosphate Chemical compound [NH4+].[NH4+].[NH4+].[NH4+].[O-]P([O-])(=O)OP([O-])([O-])=O VKFFEYLSKIYTSJ-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 150000003527 tetrahydropyrans Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 238000005936 thiocarbonylation reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0834—Compounds having one or more O-Si linkage
- C07F7/0838—Compounds with one or more Si-O-Si sequences
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/6574—Esters of oxyacids of phosphorus
- C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30001/87 | 1987-02-12 | ||
| JP3000187 | 1987-02-12 | ||
| JP33156787 | 1987-12-25 | ||
| JP331567/87 | 1987-12-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN88100826A true CN88100826A (zh) | 1988-09-14 |
Family
ID=26368254
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN198888100826A Pending CN88100826A (zh) | 1987-02-12 | 1988-02-12 | 核苷酸类似物的生产及其使用 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0278501A3 (enExample) |
| CN (1) | CN88100826A (enExample) |
| AU (1) | AU1164588A (enExample) |
| CS (1) | CS270235B2 (enExample) |
| DK (1) | DK64688A (enExample) |
| HU (1) | HUT48885A (enExample) |
| IN (1) | IN166499B (enExample) |
| NO (1) | NO880606L (enExample) |
| PL (1) | PL270564A1 (enExample) |
| YU (1) | YU28488A (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102603652A (zh) * | 2011-12-27 | 2012-07-25 | 河南师范大学 | 5-甲酰基嘧啶碳环核苷及制备方法 |
| CN104211748A (zh) * | 2013-11-15 | 2014-12-17 | 南京济群医药科技有限公司 | 6-羟基双脱氧鸟嘌呤核苷磷酸酯制备和用途 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8813148D0 (en) * | 1988-06-03 | 1988-07-06 | Glaxo Group Ltd | Chemical compounds |
| GB9204015D0 (en) | 1992-02-25 | 1992-04-08 | Wellcome Found | Therapeutic nucleosides |
| EP0577558A2 (de) * | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5874578A (en) * | 1992-07-13 | 1999-02-23 | Bristol-Myers Squibb | Process for preparing guanine-containing antiviral agents and purinyl salts useful in such process |
| CN104558080A (zh) * | 2015-02-03 | 2015-04-29 | 西安新通药物研究有限公司 | 环状磷酸酯合成的新方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5040590A (enExample) * | 1973-07-30 | 1975-04-14 | ||
| US4383114A (en) * | 1977-02-09 | 1983-05-10 | Regents Of The University Of Minnesota | Adenosine deaminase resistant antiviral purine arabinonucleosides |
-
1988
- 1988-02-02 IN IN68/MAS/88A patent/IN166499B/en unknown
- 1988-02-09 DK DK064688A patent/DK64688A/da not_active Application Discontinuation
- 1988-02-10 PL PL27056488A patent/PL270564A1/xx unknown
- 1988-02-10 HU HU88610A patent/HUT48885A/hu unknown
- 1988-02-11 NO NO880606A patent/NO880606L/no unknown
- 1988-02-11 AU AU11645/88A patent/AU1164588A/en not_active Abandoned
- 1988-02-11 EP EP19880101983 patent/EP0278501A3/en not_active Withdrawn
- 1988-02-11 YU YU00284/88A patent/YU28488A/xx unknown
- 1988-02-12 CS CS88895A patent/CS270235B2/cs unknown
- 1988-02-12 CN CN198888100826A patent/CN88100826A/zh active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102603652A (zh) * | 2011-12-27 | 2012-07-25 | 河南师范大学 | 5-甲酰基嘧啶碳环核苷及制备方法 |
| CN104211748A (zh) * | 2013-11-15 | 2014-12-17 | 南京济群医药科技有限公司 | 6-羟基双脱氧鸟嘌呤核苷磷酸酯制备和用途 |
| CN104211748B (zh) * | 2013-11-15 | 2017-05-31 | 南京济群医药科技股份有限公司 | 6‑羟基双脱氧鸟嘌呤核苷磷酸酯制备和用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| IN166499B (enExample) | 1990-05-19 |
| AU1164588A (en) | 1988-08-18 |
| DK64688D0 (da) | 1988-02-09 |
| DK64688A (da) | 1988-08-13 |
| CS89588A2 (en) | 1989-10-13 |
| EP0278501A2 (en) | 1988-08-17 |
| NO880606D0 (no) | 1988-02-11 |
| HUT48885A (en) | 1989-07-28 |
| YU28488A (en) | 1989-10-31 |
| PL270564A1 (en) | 1988-12-08 |
| EP0278501A3 (en) | 1991-01-02 |
| CS270235B2 (en) | 1990-06-13 |
| NO880606L (no) | 1988-08-15 |
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| SE01 | Entry into force of request for substantive examination | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |