CA2016765C - Antiviral, highly water soluble, stable, crystalline salts of 2',3'-dideoxyinosine monohydrate, 2',3'-dideoxy-2',3'-didehydrothymidine monohydrate and 2',3'-dideoxy-2'-fluoroinosine hemihydrate - Google Patents
Antiviral, highly water soluble, stable, crystalline salts of 2',3'-dideoxyinosine monohydrate, 2',3'-dideoxy-2',3'-didehydrothymidine monohydrate and 2',3'-dideoxy-2'-fluoroinosine hemihydrateInfo
- Publication number
- CA2016765C CA2016765C CA002016765A CA2016765A CA2016765C CA 2016765 C CA2016765 C CA 2016765C CA 002016765 A CA002016765 A CA 002016765A CA 2016765 A CA2016765 A CA 2016765A CA 2016765 C CA2016765 C CA 2016765C
- Authority
- CA
- Canada
- Prior art keywords
- salt
- dideoxy
- virus
- salt according
- stable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 40
- 229910001868 water Inorganic materials 0.000 title claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 20
- SLWSQPYUSBXANQ-BAJZRUMYSA-N 9-[(2r,3r,5s)-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound O1[C@H](CO)C[C@@H](F)[C@@H]1N1C(NC=NC2=O)=C2N=C1 SLWSQPYUSBXANQ-BAJZRUMYSA-N 0.000 title claims abstract description 7
- 230000000840 anti-viral effect Effects 0.000 title claims description 17
- TYOLIMOHEMBOPU-UOERWJHTSA-N 9-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one;hydrate Chemical class O.O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 TYOLIMOHEMBOPU-UOERWJHTSA-N 0.000 title 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims abstract description 16
- 150000001767 cationic compounds Chemical group 0.000 claims abstract 6
- 229910001411 inorganic cation Chemical group 0.000 claims abstract 6
- 241000700605 Viruses Species 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 12
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- 239000011734 sodium Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- -1 amino ion Chemical class 0.000 claims description 7
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- 239000007787 solid Substances 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 229910001413 alkali metal ion Inorganic materials 0.000 claims 4
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 claims 4
- 239000003125 aqueous solvent Substances 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 abstract description 4
- 150000002892 organic cations Chemical group 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
- 150000001875 compounds Chemical class 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- 230000003612 virological effect Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000011321 prophylaxis Methods 0.000 description 6
- 208000030507 AIDS Diseases 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
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- 208000015181 infectious disease Diseases 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 5
- 206010001513 AIDS related complex Diseases 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LAUPFIQTNKFQMT-BXXYBDJJSA-N F[C@H]1[C@@H](O[C@@H](C1)CO)N1C=NC=2C(O)=NC=NC12.[Na] Chemical compound F[C@H]1[C@@H](O[C@@H](C1)CO)N1C=NC=2C(O)=NC=NC12.[Na] LAUPFIQTNKFQMT-BXXYBDJJSA-N 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
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- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- JQZCHLQWQQFUGR-UOERWJHTSA-N 9-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one;sodium Chemical compound [Na].O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 JQZCHLQWQQFUGR-UOERWJHTSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000012901 Milli-Q water Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001768 cations Chemical group 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000713756 Caprine arthritis encephalitis virus Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 208000005599 HTLV-I Infections Diseases 0.000 description 1
- 208000007687 HTLV-II Infections Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
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- 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 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 229910017974 NH40H Inorganic materials 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000005074 Retroviridae Infections Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
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- 239000008120 corn starch Substances 0.000 description 1
- 201000003740 cowpox Diseases 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000001226 triphosphate Substances 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
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35206589A | 1989-05-15 | 1989-05-15 | |
| US352,065 | 1989-05-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2016765A1 CA2016765A1 (en) | 1990-11-15 |
| CA2016765C true CA2016765C (en) | 1997-10-21 |
Family
ID=23383649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002016765A Expired - Fee Related CA2016765C (en) | 1989-05-15 | 1990-05-14 | Antiviral, highly water soluble, stable, crystalline salts of 2',3'-dideoxyinosine monohydrate, 2',3'-dideoxy-2',3'-didehydrothymidine monohydrate and 2',3'-dideoxy-2'-fluoroinosine hemihydrate |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JP2926257B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2016765C (cg-RX-API-DMAC7.html) |
| CZ (1) | CZ9602347A3 (cg-RX-API-DMAC7.html) |
| DD (1) | DD298406A5 (cg-RX-API-DMAC7.html) |
| MY (1) | MY116824A (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ233646A (cg-RX-API-DMAC7.html) |
| PL (1) | PL163999B1 (cg-RX-API-DMAC7.html) |
| SK (2) | SK279130B6 (cg-RX-API-DMAC7.html) |
| TW (1) | TW233301B (cg-RX-API-DMAC7.html) |
| YU (1) | YU92890A (cg-RX-API-DMAC7.html) |
| ZA (1) | ZA903662B (cg-RX-API-DMAC7.html) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7122207B2 (en) | 1998-05-22 | 2006-10-17 | Bristol-Myers Squibb Company | High drug load acid labile pharmaceutical composition |
| JP4731121B2 (ja) * | 2004-02-02 | 2011-07-20 | 協和発酵キリン株式会社 | キサンチン誘導体水和物 |
| WO2009119785A1 (ja) * | 2008-03-28 | 2009-10-01 | 浜理薬品工業株式会社 | エチニルチミジン化合物の精製方法 |
| JP5485140B2 (ja) * | 2008-04-10 | 2014-05-07 | 浜理薬品工業株式会社 | ５−メチルウリジンを出発原料とするエチニルチミジン化合物の製造方法 |
-
1990
- 1990-05-11 NZ NZ23364690A patent/NZ233646A/xx unknown
- 1990-05-11 YU YU92890A patent/YU92890A/sh unknown
- 1990-05-12 TW TW79103864A patent/TW233301B/zh active
- 1990-05-14 CA CA002016765A patent/CA2016765C/en not_active Expired - Fee Related
- 1990-05-14 ZA ZA903662A patent/ZA903662B/xx unknown
- 1990-05-14 MY MYPI90000768A patent/MY116824A/en unknown
- 1990-05-14 PL PL28517590A patent/PL163999B1/pl not_active IP Right Cessation
- 1990-05-15 SK SK2372-90A patent/SK279130B6/sk unknown
- 1990-05-15 JP JP12326390A patent/JP2926257B2/ja not_active Expired - Lifetime
- 1990-05-15 DD DD90340679A patent/DD298406A5/de unknown
-
1996
- 1996-08-08 CZ CZ19962347A patent/CZ9602347A3/cs not_active IP Right Cessation
-
1997
- 1997-09-19 SK SK1273-97A patent/SK279253B6/sk unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2926257B2 (ja) | 1999-07-28 |
| CA2016765A1 (en) | 1990-11-15 |
| SK127397A3 (en) | 1998-08-05 |
| TW233301B (cg-RX-API-DMAC7.html) | 1994-11-01 |
| PL285175A1 (en) | 1991-01-14 |
| NZ233646A (en) | 1991-10-25 |
| PL163999B1 (pl) | 1994-06-30 |
| YU92890A (sh) | 1992-09-07 |
| CZ288463B6 (en) | 2001-06-13 |
| SK279253B6 (sk) | 1998-08-05 |
| JPH035477A (ja) | 1991-01-11 |
| DD298406A5 (de) | 1992-02-20 |
| CZ9602347A3 (en) | 2001-06-13 |
| SK237290A3 (en) | 1998-07-08 |
| SK279130B6 (sk) | 1998-07-08 |
| MY116824A (en) | 2004-04-30 |
| ZA903662B (en) | 1991-01-30 |
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