NO301713B1 - Krystallinske oksatiolan-derivater - Google Patents
Krystallinske oksatiolan-derivater Download PDFInfo
- Publication number
- NO301713B1 NO301713B1 NO922182A NO922182A NO301713B1 NO 301713 B1 NO301713 B1 NO 301713B1 NO 922182 A NO922182 A NO 922182A NO 922182 A NO922182 A NO 922182A NO 301713 B1 NO301713 B1 NO 301713B1
- Authority
- NO
- Norway
- Prior art keywords
- crystalline form
- cis
- oxathiolan
- pyrimidin
- amino
- Prior art date
Links
- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical class C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 title 1
- 239000013078 crystal Substances 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical group O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 15
- 238000002329 infrared spectrum Methods 0.000 claims description 12
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 8
- 238000002844 melting Methods 0.000 claims description 8
- 230000008018 melting Effects 0.000 claims description 8
- 238000010521 absorption reaction Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000011928 denatured alcohol Substances 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 5
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000032683 aging Effects 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 238000010533 azeotropic distillation Methods 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000002023 wood Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 4
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 4
- 235000011130 ammonium sulphate Nutrition 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000004296 chiral HPLC Methods 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000013067 intermediate product Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 3
- SMKDHPIQHWRJFP-UHFFFAOYSA-N (5-methoxy-1,3-oxathiolan-2-yl)methyl benzoate Chemical compound O1C(OC)CSC1COC(=O)C1=CC=CC=C1 SMKDHPIQHWRJFP-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 102100026846 Cytidine deaminase Human genes 0.000 description 2
- 108010031325 Cytidine deaminase Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000227 grinding Methods 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
- 238000000386 microscopy Methods 0.000 description 2
- 229940127073 nucleoside analogue Drugs 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 1
- OQEDEGGYERFFGP-UHFFFAOYSA-N 2-oxoethyl benzoate Chemical compound O=CCOC(=O)C1=CC=CC=C1 OQEDEGGYERFFGP-UHFFFAOYSA-N 0.000 description 1
- FLJWVVUJGVNXMZ-UHFFFAOYSA-N 2-sulfanylacetaldehyde Chemical compound SCC=O FLJWVVUJGVNXMZ-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- QYKULYCDZYBCJJ-QWHCGFSZSA-N [(2r,5s)-5-(2,4-dioxopyrimidin-1-yl)-1,3-oxathiolan-2-yl]methyl benzoate Chemical compound N1([C@H]2O[C@H](SC2)COC(=O)C=2C=CC=CC=2)C=CC(=O)NC1=O QYKULYCDZYBCJJ-QWHCGFSZSA-N 0.000 description 1
- SWOOIHFMFZUHOC-QWHCGFSZSA-N [(2r,5s)-5-(4-amino-2-oxopyrimidin-1-yl)-1,3-oxathiolan-2-yl]methyl benzoate Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](COC(=O)C=2C=CC=CC=2)SC1 SWOOIHFMFZUHOC-QWHCGFSZSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 235000019837 monoammonium phosphate Nutrition 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Secondary Cells (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919111902A GB9111902D0 (en) | 1991-06-03 | 1991-06-03 | Chemical compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO922182D0 NO922182D0 (no) | 1992-06-02 |
| NO922182L NO922182L (no) | 1992-12-04 |
| NO301713B1 true NO301713B1 (no) | 1997-12-01 |
Family
ID=10696001
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO922182A NO301713B1 (no) | 1991-06-03 | 1992-06-02 | Krystallinske oksatiolan-derivater |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US5905082A (ko) |
| EP (2) | EP0517145B1 (ko) |
| JP (1) | JP2851480B2 (ko) |
| KR (1) | KR100244008B1 (ko) |
| AP (1) | AP300A (ko) |
| AT (1) | ATE212630T1 (ko) |
| AU (2) | AU1881092A (ko) |
| BG (1) | BG60914B1 (ko) |
| CA (2) | CA2070230C (ko) |
| CZ (1) | CZ284513B6 (ko) |
| DE (1) | DE69232387T2 (ko) |
| DK (1) | DK0517145T3 (ko) |
| ES (1) | ES2171158T3 (ko) |
| GB (1) | GB9111902D0 (ko) |
| GE (1) | GEP19991834B (ko) |
| HK (1) | HK1009599A1 (ko) |
| IE (2) | IE20020782A1 (ko) |
| IL (1) | IL102073A (ko) |
| IS (2) | IS1867B (ko) |
| MX (1) | MX9202619A (ko) |
| NO (1) | NO301713B1 (ko) |
| NZ (1) | NZ242981A (ko) |
| OA (1) | OA09913A (ko) |
| PT (1) | PT517145E (ko) |
| RU (1) | RU2102393C1 (ko) |
| SG (1) | SG52455A1 (ko) |
| SK (1) | SK281249B6 (ko) |
| TW (1) | TW254939B (ko) |
| UA (1) | UA41265C2 (ko) |
| WO (1) | WO1992021676A1 (ko) |
| ZA (1) | ZA924007B (ko) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4581979A (en) * | 1983-07-01 | 1986-04-15 | Automotive Products Plc | Shipping and installation restraining clip for master cylinder input member |
| US5728575A (en) * | 1990-02-01 | 1998-03-17 | Emory University | Method of resolution of 1,3-oxathiolane nucleoside enantiomers |
| US5204466A (en) * | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| US5276151A (en) * | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
| US6642245B1 (en) | 1990-02-01 | 2003-11-04 | Emory University | Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane |
| US5444063A (en) * | 1990-12-05 | 1995-08-22 | Emory University | Enantiomerically pure β-D-dioxolane nucleosides with selective anti-Hepatitis B virus activity |
| US6812233B1 (en) | 1991-03-06 | 2004-11-02 | Emory University | Therapeutic nucleosides |
| US5817667A (en) * | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
| GB9116601D0 (en) * | 1991-08-01 | 1991-09-18 | Iaf Biochem Int | 1,3-oxathiolane nucleoside analogues |
| US6177435B1 (en) | 1992-05-13 | 2001-01-23 | Glaxo Wellcome Inc. | Therapeutic combinations |
| US20020120130A1 (en) | 1993-09-10 | 2002-08-29 | Gilles Gosselin | 2' or 3' -deoxy and 2', 3' -dideoxy-beta-L-pentofuranonucleo-side compounds, method of preparation and application in therapy, especially as anti- viral agents |
| US5587362A (en) * | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| IL115156A (en) | 1994-09-06 | 2000-07-16 | Univ Georgia | Pharmaceutical compositions for the treatment of cancer comprising 1-(2-hydroxymethyl-1,3-dioxolan-4-yl) cytosines |
| US5703058A (en) | 1995-01-27 | 1997-12-30 | Emory University | Compositions containing 5-fluoro-2',3'-didehydro-2',3'-dideoxycytidine or a mono-, di-, or triphosphate thereof and a second antiviral agent |
| US6391859B1 (en) | 1995-01-27 | 2002-05-21 | Emory University | [5-Carboxamido or 5-fluoro]-[2′,3′-unsaturated or 3′-modified]-pyrimidine nucleosides |
| US5808040A (en) * | 1995-01-30 | 1998-09-15 | Yale University | L-nucleosides incorporated into polymeric structure for stabilization of oligonucleotides |
| EP0831852B1 (en) | 1995-06-07 | 2006-11-29 | Emory University | Nucleosides with anti-hepatitis b virus activity |
| US5914332A (en) * | 1995-12-13 | 1999-06-22 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| BR9709939A (pt) | 1996-06-25 | 1999-08-10 | Glaxo Group Ltd | Combinação formulação farmacêutica processo de tratamento de uma infecção por hiv em um animal infectado usos de éster tetraidro-3-furanila do ácido 3s[3r*(1r*,2s*)]-[-3-[[4-amino-fenil)sulfonil](2-metilprop ril)-amino]-2-hidroxi-1-fenilmetil)propil]-carbâmico de zidovudina e de (2r,cis)-4-amino-1-(2-hidroximetil-1,3-oxatiolan-5-il)-(1h)-pirimidin-2-ona e pacote para paciente |
| US5753789A (en) * | 1996-07-26 | 1998-05-19 | Yale University | Oligonucleotides containing L-nucleosides |
| TW536403B (en) * | 1997-03-24 | 2003-06-11 | Glaxo Group Ltd | An ethanol and ethylenediaminetetraacetic acid free pharmaceutical composition comprising lamivudine and exhibiting antimicrobial preservative efficacy |
| US6436948B1 (en) | 2000-03-03 | 2002-08-20 | University Of Georgia Research Foundation Inc. | Method for the treatment of psoriasis and genital warts |
| DK1389207T3 (da) * | 2001-03-01 | 2006-04-18 | Gilead Sciences Inc | Polymorfe og andre krystallinske former af cis-FTC |
| CA2351049C (en) | 2001-06-18 | 2007-03-13 | Brantford Chemicals Inc. | Process for recovery of the desired cis-1,3-oxathiolane nucleosides from their undesired trans-isomers |
| WO2003027106A1 (en) * | 2001-09-25 | 2003-04-03 | Cadila Healthcar Limited | Process for the preparation of crystalline polymorph ii of lamivudine |
| IL163666A0 (en) | 2002-02-22 | 2005-12-18 | New River Pharmaceuticals Inc | Active agent delivery systems and methods for protecting and administering active agents |
| WO2004043433A2 (en) * | 2002-11-08 | 2004-05-27 | Glaxo Group Limited | Pharmaceutical antiviral compositions |
| KR20090053867A (ko) | 2003-01-14 | 2009-05-27 | 길리애드 사이언시즈, 인코포레이티드 | 복합 항바이러스 치료를 위한 조성물 및 방법 |
| PT1809662E (pt) * | 2004-11-10 | 2009-02-26 | Novartis Vaccines & Diagnostic | Interferão beta desamidado |
| US20060242012A1 (en) * | 2005-04-22 | 2006-10-26 | Sumit Agarwal | Determining or scoring properties to solicit to join ad network using advertiser or aggregated advertiser interest |
| TWI471145B (zh) | 2005-06-13 | 2015-02-01 | Bristol Myers Squibb & Gilead Sciences Llc | 單一式藥學劑量型 |
| TWI375560B (en) | 2005-06-13 | 2012-11-01 | Gilead Sciences Inc | Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same |
| EP2007758B1 (en) | 2006-04-18 | 2010-10-20 | Lupin Ltd. | A novel crystalline form of lamivudine |
| AR068374A1 (es) * | 2007-09-06 | 2009-11-11 | Combino Pharm Sl | Nuevas composiciones farmaceuticas del complejo lamivudina beta - ciclodextrina |
| WO2009037538A2 (en) * | 2007-09-17 | 2009-03-26 | Aurobindo Pharma Ltd | Process for the preparation of lamivudine form i |
| AU2008331168A1 (en) * | 2007-11-29 | 2009-06-04 | Ranbaxy Laboratories Limited | Crystalline form I of lamivudine and its preparation |
| US20100311970A1 (en) * | 2007-11-29 | 2010-12-09 | Ranbaxy Laboratories Limited | Process for the preparation of substituted 1,3-oxathiolanes |
| AU2008331167A1 (en) * | 2007-11-29 | 2009-06-04 | Ranbaxy Laboratories Limited | Process and intermediates for the preparation of substituted 1, 3-oxathiolanes, especially lamivudine |
| WO2009127996A1 (en) * | 2008-04-17 | 2009-10-22 | Ranbaxy Laboratories Limited | Novel crystalline form of lamivudine |
| WO2010023676A2 (en) * | 2008-09-01 | 2010-03-04 | Hetero Research Foundation | Process for preparing lamivudine polymorph form |
| WO2010055526A1 (en) * | 2008-11-12 | 2010-05-20 | Lupin Limited | A novel polymorph of emtricitabine and a process for preparing of the same |
| CN101531656B (zh) * | 2009-03-24 | 2010-12-08 | 福建广生堂药业有限公司 | 拉米夫定晶型及其制备方法 |
| CN101993439B (zh) * | 2009-03-24 | 2013-04-24 | 福建广生堂药业股份有限公司 | 拉米夫定晶型及其制备方法 |
| EP2435052B1 (en) * | 2009-05-27 | 2015-07-15 | Hetero Research Foundation | Solid oral dosage forms of lamivudine with isomalt |
| WO2011007367A1 (en) | 2009-07-15 | 2011-01-20 | Lupin Limited | An improved process for preparation of efavirenz |
| DK2488516T3 (en) | 2009-10-14 | 2015-05-26 | Mylan Lab Ltd | Method of producing lamivudine and novel salts in the preparation thereof |
| ES2969969T3 (es) | 2010-01-27 | 2024-05-23 | Viiv Healthcare Co | Combinaciones de dolutegravir y lamivudina para el tratamiento de la infección por VIH |
| US20120295930A1 (en) * | 2010-02-03 | 2012-11-22 | Shankar Rama | Novel process for the preparation of cis-nucleoside derivative |
| EP2536715A1 (en) | 2010-02-12 | 2012-12-26 | Merck Sharp & Dohme Corp. | Preparation of lamivudine form i |
| EP2579892A2 (en) | 2010-06-09 | 2013-04-17 | Vaccine Technologies, Incorporated | Therapeutic immunization in hiv infected subjects receiving stable antiretroviral treatment |
| US20130296562A1 (en) | 2011-08-05 | 2013-11-07 | Lupin Limited | Stereoselective process for preparation of 1,3-oxathiolane nucleosides |
| WO2013168066A1 (en) | 2012-05-05 | 2013-11-14 | Lupin Limited | An improved process for the manufacture of lamivudine form i. |
| CN114099454B (zh) * | 2020-08-31 | 2023-06-27 | 长春海悦药业股份有限公司 | 一种拉米夫定片及其制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5047407A (en) * | 1989-02-08 | 1991-09-10 | Iaf Biochem International, Inc. | 2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties |
| US5204466A (en) * | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| GB9009861D0 (en) * | 1990-05-02 | 1990-06-27 | Glaxo Group Ltd | Chemical compounds |
| US5248776A (en) * | 1990-12-05 | 1993-09-28 | University Of Georgia Research Foundation, Inc. | Process for enantiomerically pure β-L-1,3-oxathiolane nucleosides |
| US5179104A (en) * | 1990-12-05 | 1993-01-12 | University Of Georgia Research Foundation, Inc. | Process for the preparation of enantiomerically pure β-D-(-)-dioxolane-nucleosides |
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