NL192793C - Deoxyuridinederivaten met antivirale werking; werkwijze voor de bereiding daarvan en geneesmiddel tegen virusziekten. - Google Patents
Deoxyuridinederivaten met antivirale werking; werkwijze voor de bereiding daarvan en geneesmiddel tegen virusziekten. Download PDFInfo
- Publication number
- NL192793C NL192793C NL7903029A NL7903029A NL192793C NL 192793 C NL192793 C NL 192793C NL 7903029 A NL7903029 A NL 7903029A NL 7903029 A NL7903029 A NL 7903029A NL 192793 C NL192793 C NL 192793C
- Authority
- NL
- Netherlands
- Prior art keywords
- deoxiuridine
- bromovinyl
- antiviral
- iodovinyl
- deoxy
- Prior art date
Links
- 230000000840 anti-viral effect Effects 0.000 title claims description 24
- 238000002360 preparation method Methods 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 9
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 title description 3
- 239000003443 antiviral agent Substances 0.000 title description 2
- -1 2-bromovinyl Chemical group 0.000 claims description 39
- 150000001875 compounds Chemical class 0.000 claims description 33
- 210000004027 cell Anatomy 0.000 claims description 26
- 241000700605 Viruses Species 0.000 claims description 22
- 238000004113 cell culture Methods 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 16
- 208000009889 Herpes Simplex Diseases 0.000 claims description 9
- ODZBBRURCPAEIQ-PIXDULNESA-N helpin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(\C=C\Br)=C1 ODZBBRURCPAEIQ-PIXDULNESA-N 0.000 claims description 8
- 241000700584 Simplexvirus Species 0.000 claims description 7
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 6
- 210000003292 kidney cell Anatomy 0.000 claims description 6
- YAAQOXBNCODRSI-DJLDLDEBSA-N 5-ethenyl-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C=C)=C1 YAAQOXBNCODRSI-DJLDLDEBSA-N 0.000 claims description 5
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- LOLNFJHUEIDGNH-PIXDULNESA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(e)-2-iodoethenyl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(\C=C\I)=C1 LOLNFJHUEIDGNH-PIXDULNESA-N 0.000 claims description 4
- CDEURGJCGCHYFH-DJLDLDEBSA-N 5-ethynyl-2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C#C)=C1 CDEURGJCGCHYFH-DJLDLDEBSA-N 0.000 claims description 4
- 230000001399 anti-metabolic effect Effects 0.000 claims description 4
- 230000000120 cytopathologic effect Effects 0.000 claims description 4
- 238000012360 testing method Methods 0.000 claims description 3
- 208000031295 Animal disease Diseases 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 239000000654 additive Substances 0.000 claims 1
- 239000003125 aqueous solvent Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 150000005690 diesters Chemical class 0.000 claims 1
- 239000002270 dispersing agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000975 dye Substances 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 210000004400 mucous membrane Anatomy 0.000 claims 1
- 239000002674 ointment Substances 0.000 claims 1
- 239000006072 paste Substances 0.000 claims 1
- 239000002304 perfume Substances 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 239000000375 suspending agent Substances 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 239000000080 wetting agent Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 229920002554 vinyl polymer Polymers 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 7
- BLXGZIDBSXVMLU-OWOJBTEDSA-N 5-[(e)-2-bromoethenyl]-1h-pyrimidine-2,4-dione Chemical compound Br\C=C\C1=CNC(=O)NC1=O BLXGZIDBSXVMLU-OWOJBTEDSA-N 0.000 description 6
- KTZDXHJATZVCLY-OWOJBTEDSA-N 5-[(e)-2-iodoethenyl]-1h-pyrimidine-2,4-dione Chemical compound I\C=C\C1=CNC(=O)NC1=O KTZDXHJATZVCLY-OWOJBTEDSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 241000700618 Vaccinia virus Species 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 125000004665 trialkylsilyl group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- FQRIBMHYAICHAB-DJLDLDEBSA-N 5-(1-chloroethenyl)-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(Cl)=C)=C1 FQRIBMHYAICHAB-DJLDLDEBSA-N 0.000 description 2
- ZRYZBEQILKESAW-UHFFFAOYSA-N 5-ethenyl-1h-pyrimidine-2,4-dione Chemical compound C=CC1=CNC(=O)NC1=O ZRYZBEQILKESAW-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 125000005440 p-toluyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C(*)=O)C([H])([H])[H] 0.000 description 2
- 210000001626 skin fibroblast Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- 210000003501 vero cell Anatomy 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-BIIVOSGPSA-N 2'-deoxythymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-BIIVOSGPSA-N 0.000 description 1
- PDWIQYODPROSQH-PYHARJCCSA-N 2-deoxy-D-ribofuranose Chemical compound OC[C@H]1OC(O)C[C@@H]1O PDWIQYODPROSQH-PYHARJCCSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000867607 Chlorocebus sabaeus Species 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
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
- C07H19/06—Pyrimidine 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
-
- 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
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1615978 | 1978-04-24 | ||
| GB16158/78A GB1601020A (en) | 1978-04-24 | 1978-04-24 | 2'-deoxy-5 (2-halogenovinyl)-uridines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NL7903029A NL7903029A (nl) | 1979-10-26 |
| NL192793B NL192793B (nl) | 1997-10-01 |
| NL192793C true NL192793C (nl) | 1998-02-03 |
Family
ID=10072234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL7903029A NL192793C (nl) | 1978-04-24 | 1979-04-18 | Deoxyuridinederivaten met antivirale werking; werkwijze voor de bereiding daarvan en geneesmiddel tegen virusziekten. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4424211A (es) |
| JP (1) | JPS554364A (es) |
| BE (1) | BE875773A (es) |
| CA (1) | CA1117108A (es) |
| CH (1) | CH643273A5 (es) |
| DE (1) | DE2915254A1 (es) |
| FR (1) | FR2432526A1 (es) |
| GB (1) | GB1601020A (es) |
| IT (1) | IT1165954B (es) |
| NL (1) | NL192793C (es) |
| SE (1) | SE445832B (es) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5687599A (en) * | 1979-12-19 | 1981-07-16 | Yamasa Shoyu Co Ltd | E 55 22halogenovinyl arabinofuranosyluracil and its preparation |
| US4383990A (en) * | 1980-10-01 | 1983-05-17 | Beecham Group Limited | Antiviral agents, their preparation and use |
| EP0060099A1 (en) * | 1981-03-11 | 1982-09-15 | Beecham Group Plc | Antiviral agents, their preparation and use |
| NZ199764A (en) * | 1981-03-20 | 1984-08-24 | Beecham Group Plc | 5-(2-halogenovinyl)-2'-deoxyuridine derivatives and pharmaceutical compositions |
| EP0072137A1 (en) * | 1981-08-01 | 1983-02-16 | Beecham Group Plc | Antiviral deoxyuridine compounds |
| HU183567B (en) * | 1981-09-07 | 1984-05-28 | Mta Koezponti Kemiai Kutato In | Process for preparing /e/-5-/2-bromo-vinyl/-uridine and derivatives thereof |
| EP0082667A1 (en) * | 1981-12-18 | 1983-06-29 | Beecham Group Plc | Pharmaceutical compositions |
| EP0088501B1 (en) * | 1982-02-12 | 1986-04-16 | United Kingdom Atomic Energy Authority | Laser pipe welder/cutter |
| EP0095292A1 (en) * | 1982-05-22 | 1983-11-30 | Beecham Group Plc | 5-(2-halogenovinyl)-2'-deoxyuridine derivatives, processes for their preparation, pharmaceutical compositions containing them, and their use in treating viral infections" |
| EP0095294A1 (en) * | 1982-05-22 | 1983-11-30 | Beecham Group Plc | Deoxyuridine compounds, methods for preparing them and their use in medicine |
| EP0097039A1 (en) * | 1982-06-16 | 1983-12-28 | Beecham Group Plc | 5-(E-2-halovinyl)-2'-deoxyuridine derivatives, processes for their preparation, pharmaceutical compositions containing them, and their use in treating viral infections |
| HU187736B (en) * | 1982-08-04 | 1986-02-28 | Mta Koezponti Kemiai Kutato Intezet,Hu | Process for producing /e/ -5-/2-bromovinyl/-2-comma above-deoxyuridine and o-acyl derivatives |
| FI832884A (fi) * | 1982-08-17 | 1984-02-18 | Sandoz Ag | Desoxiuridinderivat, deras framstaellningsfoerfaranden och anvaendning som farmaceutiska medel |
| CA1257595A (en) * | 1982-09-17 | 1989-07-18 | Glaxo Group Ltd | 5-HALOGEROVINYL-2'-DESOXYURIDINE DERIVATIVES |
| EP0104857A1 (en) * | 1982-09-28 | 1984-04-04 | Beecham Group Plc | Deoxyuridine compounds, methods for preparing them and their use in medicine |
| US4658044A (en) * | 1983-09-16 | 1987-04-14 | Glaxo Group Limited | Intermediates for uracil derivatives |
| EP0195805A4 (en) * | 1984-09-24 | 1987-07-09 | Scm Corp | PROCESS FOR THE PREPARATION OF 2-DESOXYURIDINE. |
| GB8517402D0 (en) * | 1985-07-10 | 1985-08-14 | Wellcome Found | Treatment of viral infections |
| GB8629892D0 (en) * | 1986-12-15 | 1987-01-28 | Wellcome Found | Antiviral compounds |
| US5215971A (en) * | 1986-12-19 | 1993-06-01 | Medivir Ab | Antiviral pharmaceutical composition comprising 5-substituted pyrimidine nucleosides |
| SE8605503D0 (sv) * | 1986-12-19 | 1986-12-19 | Astra Laekemedel Ab | Novel medicinal use |
| US4863927A (en) * | 1987-05-11 | 1989-09-05 | Merck & Co., Inc. | 1-(2-hydroxymethyl)cycloalkylmethyl)-5-substituted uracils |
| JPH0217199A (ja) * | 1988-07-05 | 1990-01-22 | Japan Tobacco Inc | ２’−デオキシ−β−アデノシンの製造方法 |
| JPH0217198A (ja) * | 1988-07-05 | 1990-01-22 | Japan Tobacco Inc | ２’−デオキシ−β−シチジン誘導体およびその塩の製造法 |
| WO1990001324A1 (en) * | 1988-08-10 | 1990-02-22 | Stephen Leslie Sacks | PRODUCTION OF RADIOIODINATED 1-β-D-ARABINOFURANOSYL)-5(E)-(2-IODOVINYL)URACIL, AND USES THEREOF, AND RELATED ANALOGUES INCORPORATING ALTERNATIVE HALOGEN RADIONUCLIDES, THE GENERAL RADIOHALOGENATION PRECURSORS, 1-(2,3,5-TRI-O-ACETYL-β-D-ARABINOFURANOSYL)-5(Z and E)-(2-TRIMETHYLSILYLVINYL)URACIL, PROCESSES FOR RADIOHA |
| EA005497B1 (ru) * | 2001-01-03 | 2005-02-24 | Берлин Хеми Аг | Применение фармацевтической композиции, содержащей бривудин, для лечения герпесвирусных инфекций |
| DE10109657A1 (de) * | 2001-02-28 | 2002-09-05 | Menarini Ricerche Spa | Verfahren zur Herstellung von (E)-5-(2-Bromvinyl)-2`-desoxyuridin |
| JP4651942B2 (ja) * | 2001-12-20 | 2011-03-16 | フアーマセツト・インコーポレイテッド | Ｅｂｖ及びｋｈｓｖ感染並びにそれに伴う異常細胞増殖の治療 |
| CN102432655A (zh) * | 2011-10-28 | 2012-05-02 | 河南师范大学 | 一种合成5-((e)-2-溴乙烯基)-2′-脱氧尿嘧啶核苷(溴呋啶)的方法 |
| EP3792271A1 (en) | 2019-09-13 | 2021-03-17 | Aurobindo Pharma Limited | A process for the preparation of brivudine |
| WO2021209563A1 (en) | 2020-04-16 | 2021-10-21 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU452961A3 (ru) | 1969-04-11 | 1974-12-05 | Шеринг Аг. (Фирма) | Способ получени пиримидиннуклеозидов |
| DE2012888C3 (de) | 1970-03-14 | 1981-04-02 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 5-Azapyrimidinnucleosiden |
| DE2122991C2 (de) | 1971-05-04 | 1982-06-09 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von Cytosin- und 6-Azacytosinnucleosiden |
| US4093715A (en) | 1977-04-28 | 1978-06-06 | Research Corporation | 5-Iodo-5'-amino-2',5'-dideoxycytidine and the pharmaceutically acceptable salts thereof |
| US4093716A (en) | 1977-04-28 | 1978-06-06 | Research Corporation | Compositions containing 5-amino-5-deoxythymidine and pharmaceutically acceptable salts thereof |
| DE2721466A1 (de) | 1977-05-12 | 1978-11-16 | Robugen Gmbh | Verfahren zur herstellung von 2'-desoxyribofuranosylnucleosiden |
-
1978
- 1978-04-24 GB GB16158/78A patent/GB1601020A/en not_active Expired
-
1979
- 1979-04-14 DE DE19792915254 patent/DE2915254A1/de active Granted
- 1979-04-18 NL NL7903029A patent/NL192793C/nl not_active IP Right Cessation
- 1979-04-19 CH CH367179A patent/CH643273A5/de not_active IP Right Cessation
- 1979-04-23 FR FR7910230A patent/FR2432526A1/fr active Granted
- 1979-04-23 IT IT09403/79A patent/IT1165954B/it active
- 1979-04-23 CA CA000326164A patent/CA1117108A/en not_active Expired
- 1979-04-23 BE BE1/9368A patent/BE875773A/xx not_active IP Right Cessation
- 1979-04-23 SE SE7903541A patent/SE445832B/sv not_active IP Right Cessation
- 1979-04-24 JP JP5133379A patent/JPS554364A/ja active Granted
-
1981
- 1981-12-21 US US06/332,757 patent/US4424211A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| IT1165954B (it) | 1987-04-29 |
| GB1601020A (en) | 1981-10-21 |
| DE2915254C2 (es) | 1990-07-12 |
| SE7903541L (sv) | 1979-10-25 |
| DE2915254A1 (de) | 1979-11-15 |
| FR2432526B1 (es) | 1982-10-08 |
| US4424211A (en) | 1984-01-03 |
| FR2432526A1 (fr) | 1980-02-29 |
| IT7909403A0 (it) | 1979-04-23 |
| NL7903029A (nl) | 1979-10-26 |
| CA1117108A (en) | 1982-01-26 |
| NL192793B (nl) | 1997-10-01 |
| JPS642599B2 (es) | 1989-01-18 |
| BE875773A (nl) | 1979-10-23 |
| JPS554364A (en) | 1980-01-12 |
| SE445832B (sv) | 1986-07-21 |
| CH643273A5 (de) | 1984-05-30 |
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| BC | A request for examination has been filed | ||
| V4 | Discontinued because of reaching the maximum lifetime of a patent |
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