KR100244008B1 - 결정질 옥사티올란 유도체 - Google Patents
결정질 옥사티올란 유도체 Download PDFInfo
- Publication number
- KR100244008B1 KR100244008B1 KR1019920009537A KR920009537A KR100244008B1 KR 100244008 B1 KR100244008 B1 KR 100244008B1 KR 1019920009537 A KR1019920009537 A KR 1019920009537A KR 920009537 A KR920009537 A KR 920009537A KR 100244008 B1 KR100244008 B1 KR 100244008B1
- Authority
- KR
- South Korea
- Prior art keywords
- cis
- amino
- oxathiolan
- hydroxymethyl
- crystalline form
- 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 - Lifetime
Links
- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical class C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 title 1
- 240000007124 Brassica oleracea Species 0.000 claims abstract description 9
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 claims abstract description 9
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 claims abstract description 9
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 23
- 239000013078 crystal Substances 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 12
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 10
- 238000002844 melting Methods 0.000 claims description 8
- 230000008018 melting Effects 0.000 claims description 8
- 238000010521 absorption reaction Methods 0.000 claims description 6
- 238000002329 infrared spectrum Methods 0.000 claims description 5
- 239000011928 denatured alcohol Substances 0.000 claims description 4
- 230000032683 aging Effects 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000004599 antimicrobial Substances 0.000 claims 3
- 239000012736 aqueous medium Substances 0.000 claims 3
- 235000002566 Capsicum Nutrition 0.000 claims 1
- 239000006002 Pepper Substances 0.000 claims 1
- 235000016761 Piper aduncum Nutrition 0.000 claims 1
- 235000017804 Piper guineense Nutrition 0.000 claims 1
- 244000203593 Piper nigrum Species 0.000 claims 1
- 235000008184 Piper nigrum Nutrition 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 230000011987 methylation Effects 0.000 claims 1
- 238000007069 methylation reaction Methods 0.000 claims 1
- 235000015096 spirit Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- XAVAVWGQHMMKGM-JGVFFNPUSA-N [(2r,5s)-5-(4-amino-2h-pyrimidin-1-yl)-1,3-oxathiolan-2-yl]methanol Chemical compound C1=CC(N)=NCN1[C@H]1O[C@@H](CO)SC1 XAVAVWGQHMMKGM-JGVFFNPUSA-N 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 31
- 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
- 239000000203 mixture Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 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 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
- 238000010586 diagram Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- LHBJRSXVTINARH-UHFFFAOYSA-N (5-methoxy-1,3-oxathiolan-2-yl)methanol Chemical compound COC1CSC(CO)O1 LHBJRSXVTINARH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229940079832 sodium starch glycolate Drugs 0.000 description 3
- 229920003109 sodium starch glycolate Polymers 0.000 description 3
- 239000008109 sodium starch glycolate Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- 229910002483 Cu Ka Inorganic materials 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
- 239000007983 Tris buffer Substances 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling 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
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 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
- 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
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-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
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 235000002567 Capsicum annuum Nutrition 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 241000700605 Viruses Species 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
- 125000000218 acetic acid group Chemical group C(C)(=O)* 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
- 125000004429 atom Chemical group 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012230 colorless oil Substances 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
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 231100000676 disease causative agent Toxicity 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
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- -1 ethanol Chemical class 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
- 238000000227 grinding Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 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
- 239000008176 lyophilized powder 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
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000019837 monoammonium phosphate Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000013022 venting Methods 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)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9111902.4 | 1991-06-03 | ||
| GB919111902A GB9111902D0 (en) | 1991-06-03 | 1991-06-03 | Chemical compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR930000511A KR930000511A (ko) | 1993-01-15 |
| KR100244008B1 true KR100244008B1 (ko) | 2000-03-02 |
Family
ID=10696001
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019920009537A Expired - Lifetime KR100244008B1 (ko) | 1991-06-03 | 1992-06-02 | 결정질 옥사티올란 유도체 |
Country Status (30)
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 |
| 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 |
| US5204466A (en) * | 1990-02-01 | 1993-04-20 | Emory University | Method and compositions for the synthesis of bch-189 and related compounds |
| US6069252A (en) | 1990-02-01 | 2000-05-30 | Emory University | Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers |
| 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 |
| ES2276404T3 (es) | 1995-06-07 | 2007-06-16 | Emory University | Nucleosidos con actividad antivirus de la hepatitis-b. |
| US5914332A (en) * | 1995-12-13 | 1999-06-22 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| KR20000022226A (ko) | 1996-06-25 | 2000-04-25 | 그레이엄 브레레톤;레슬리 에드워즈 | Hiv 치료에 사용하기 위한 vx478, 지도부딘, ftc 및(또는) 3tc를 포함하는 배합물 |
| 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 |
| ATE383355T1 (de) | 2001-03-01 | 2008-01-15 | Abbott Lab | Polymorph und andere kristallinische formen von zusammen-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 |
| EP2316468A1 (en) | 2002-02-22 | 2011-05-04 | Shire LLC | Delivery system and methods for protecting and administering dextroamphetamine |
| ATE361059T1 (de) * | 2002-11-08 | 2007-05-15 | Glaxo Group Ltd | Antivirale zusammensetzungen |
| PT1583542E (pt) | 2003-01-14 | 2008-09-17 | Gilead Sciences Inc | Composições e métodos para terapia de combinação antiviral |
| DE602005011321D1 (de) * | 2004-11-10 | 2009-01-08 | Novartis Vaccines & Diagnostic | Deamidiertes interferon-beta |
| 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 |
| AU2007237818B2 (en) * | 2006-04-18 | 2012-09-27 | Lupin Limited | A novel crystalline form of lamivudine |
| US20090068267A1 (en) * | 2007-09-06 | 2009-03-12 | Combino Pharm, S.L. | Novel Pharmaceutical Compositions |
| WO2009037538A2 (en) * | 2007-09-17 | 2009-03-26 | Aurobindo Pharma Ltd | Process for the preparation of lamivudine form i |
| SI2225232T1 (sl) * | 2007-11-29 | 2012-12-31 | Ranbaxy Laboratories Limited | Postopek za pripravo substituiranih 1,3-oksatiolanov |
| CN101918416A (zh) * | 2007-11-29 | 2010-12-15 | 兰贝克赛实验室有限公司 | 制备取代的1,3-氧硫杂环戊烷,尤其是拉米夫定的方法和中间体 |
| WO2009069013A1 (en) * | 2007-11-29 | 2009-06-04 | Ranbaxy Laboratories Limited | Crystalline form i of lamivudine and its preparation |
| WO2009127996A1 (en) * | 2008-04-17 | 2009-10-22 | Ranbaxy Laboratories Limited | Novel crystalline form of lamivudine |
| EP2318398A4 (en) | 2008-09-01 | 2011-12-07 | Hetero Research Foundation | PROCESS FOR PREPARING A POLYMORPHIC FORM OF LAMIVUDIN |
| US20110288298A1 (en) * | 2008-11-12 | 2011-11-24 | Lupin Limited | novel polymorph of emtricitabine and a process for preparing of the same |
| 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 |
| 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 |
| WO2010137027A1 (en) * | 2009-05-27 | 2010-12-02 | Hetero Research Foundation | Solid oral dosage forms of lamivudine |
| US8710218B2 (en) | 2009-07-15 | 2014-04-29 | Lupin Limited | Process for preparation of Efavirenz |
| WO2011045815A2 (en) | 2009-10-14 | 2011-04-21 | Matrix Laboratories Ltd. | Process for the preparation of lamivudine and novel salts in the manufacture thereof |
| EP3351249A1 (en) | 2010-01-27 | 2018-07-25 | VIIV Healthcare Company | Antiviral therapy |
| WO2011095987A1 (en) * | 2010-02-03 | 2011-08-11 | Matrix Laboratories Ltd. | Novel process for the preparation of cis-nucleoside derivative |
| AU2011215878A1 (en) | 2010-02-12 | 2012-08-09 | Merck Sharp & Dohme Corp. | Preparation of lamivudine Form I |
| CN114010776A (zh) | 2010-06-09 | 2022-02-08 | 疫苗技术股份有限公司 | 用于增强抗逆转录病毒治疗的hiv感染者的治疗性免疫 |
| WO2013021290A1 (en) | 2011-08-05 | 2013-02-14 | Lupin Limited | A 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0382526A2 (en) * | 1989-02-08 | 1990-08-16 | Biochem Pharma Inc | Substituted -1,3-oxathiolanes with antiviral properties |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ228645A (en) * | 1988-04-11 | 1991-09-25 | Iaf Biochem Int | 1,3-dioxolane derivatives substituted in the 5th position by a purine or pyrimidine radical; treatment of viral infections |
| 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 |
| JPH04358486A (ja) * | 1991-06-04 | 1992-12-11 | Toshiba Corp | 高能率符号化信号処理装置 |
-
1991
- 1991-06-03 GB GB919111902A patent/GB9111902D0/en active Pending
-
1992
- 1992-02-06 UA UA93004068A patent/UA41265C2/uk unknown
- 1992-06-02 JP JP4166809A patent/JP2851480B2/ja not_active Expired - Lifetime
- 1992-06-02 US US07/892,029 patent/US5905082A/en not_active Expired - Lifetime
- 1992-06-02 CA CA002311988A patent/CA2311988C/en not_active Expired - Lifetime
- 1992-06-02 DE DE69232387T patent/DE69232387T2/de not_active Expired - Lifetime
- 1992-06-02 AU AU17361/92A patent/AU656379B2/en not_active Expired
- 1992-06-02 SG SG1996004763A patent/SG52455A1/en unknown
- 1992-06-02 MX MX9202619A patent/MX9202619A/es active IP Right Grant
- 1992-06-02 WO PCT/EP1992/001213 patent/WO1992021676A1/en not_active Ceased
- 1992-06-02 EP EP92109221A patent/EP0517145B1/en not_active Expired - Lifetime
- 1992-06-02 ES ES92109221T patent/ES2171158T3/es not_active Expired - Lifetime
- 1992-06-02 AT AT92109221T patent/ATE212630T1/de active
- 1992-06-02 CA CA002070230A patent/CA2070230C/en not_active Expired - Lifetime
- 1992-06-02 PT PT92109221T patent/PT517145E/pt unknown
- 1992-06-02 IL IL10207392A patent/IL102073A/en not_active IP Right Cessation
- 1992-06-02 AU AU18810/92A patent/AU1881092A/en not_active Abandoned
- 1992-06-02 RU RU93058495A patent/RU2102393C1/ru active
- 1992-06-02 EP EP01200491A patent/EP1099700A1/en not_active Withdrawn
- 1992-06-02 IS IS3873A patent/IS1867B/is unknown
- 1992-06-02 DK DK92109221T patent/DK0517145T3/da active
- 1992-06-02 ZA ZA924007A patent/ZA924007B/xx unknown
- 1992-06-02 GE GEAP19922654A patent/GEP19991834B/en unknown
- 1992-06-02 TW TW081104300A patent/TW254939B/zh not_active IP Right Cessation
- 1992-06-02 SK SK1257-93A patent/SK281249B6/sk not_active IP Right Cessation
- 1992-06-02 NO NO922182A patent/NO301713B1/no not_active IP Right Cessation
- 1992-06-02 KR KR1019920009537A patent/KR100244008B1/ko not_active Expired - Lifetime
- 1992-06-02 AP APAP/P/1992/000395A patent/AP300A/en active
- 1992-06-02 NZ NZ242981A patent/NZ242981A/en not_active IP Right Cessation
- 1992-06-02 CZ CS932612A patent/CZ284513B6/cs not_active IP Right Cessation
- 1992-07-01 IE IE20020782A patent/IE20020782A1/en not_active IP Right Cessation
- 1992-07-01 IE IE178092A patent/IE921780A1/en not_active IP Right Cessation
- 1992-12-04 IS IS4268A patent/IS4268A/is unknown
-
1993
- 1993-11-15 OA OA60437A patent/OA09913A/en unknown
- 1993-11-30 BG BG98254A patent/BG60914B1/bg unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0382526A2 (en) * | 1989-02-08 | 1990-08-16 | Biochem Pharma Inc | Substituted -1,3-oxathiolanes with antiviral properties |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2102393C1 (ru) | (-)-цис-4-амино-1-(2-оксиметил-1,3-оксатиолан-5-ил-(1н)-пиримидин-2-он в кристаллических формах, способы их получения и фармацевтическая композиция | |
| IE83503B1 (en) | Crystalline oxathiolane derivatives | |
| TWI222448B (en) | 1,3-oxathiolane nucleoside analogues | |
| US20150368286A1 (en) | Methods of preparing substituted nucleotide analogs | |
| RU2684402C2 (ru) | Новый тип производного цитидина и его применение | |
| SK391091A3 (en) | Crystalline paroxetine hydrochloride hemihydrate, pharmacuetical composition containing the same and its use | |
| CS265248B2 (en) | Process for preparing analogs of rebeccamycine | |
| EP1844062A2 (en) | Inhibitors of dna methyltransferase | |
| JP2002538144A (ja) | 抗ウイルス性２，４−ピリミジンジオン誘導体およびその製造方法 | |
| BRPI0207652B1 (pt) | avermectinas substituídas na posiçao 4" tendo propriedades pesticidas | |
| CN109843300B (zh) | 一种化合物的结晶多晶型形式 | |
| CA2867970A1 (en) | Polymorphic and other crystalline forms of cis-ftc | |
| US5463078A (en) | Anisomycin derivatives and anticancer agents, antifungal agents and antiprotozoan agents containing the same | |
| KR0119908B1 (ko) | 3(2h)-푸란온 유도체 | |
| US4859680A (en) | Pyrimidine derivatives as antiviral compounds | |
| HU187600B (en) | Process for preparing 2-methyl-9,10-didehydro-ergolines | |
| HK1009599B (en) | Crystalline oxathiolane derivatives | |
| KR0140021B1 (ko) | 피리미딘 아사이클로뉴클레오시드 유도체 | |
| EP0601520A1 (en) | Trifluorothymidine derivatives, process for producing the same and anti-cancer agent containing the same | |
| CN105052936B (zh) | N‑苯磺酰基‑3‑(2‑基‑乙酰基)‑6‑甲基吲哚类衍生物的用途 | |
| KR20010006730A (ko) | 신규한 항바이러스성 2,4-피리미딘디온 유도체 | |
| MC1264A1 (fr) | Procede de preparation de benzylpyrimides et de medicaments contenant ces substances | |
| US20160194281A1 (en) | Crystalline forms of silodosin | |
| NO172582B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive estere og amider av nukleosid-derivater |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 19920602 |
|
| AMND | Amendment | ||
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 19970530 Comment text: Request for Examination of Application Patent event code: PA02011R01I Patent event date: 19920602 Comment text: Patent Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 19990327 Patent event code: PE09021S01D |
|
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 19990729 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 19990327 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |
|
| J201 | Request for trial against refusal decision | ||
| PJ0201 | Trial against decision of rejection |
Patent event date: 19990830 Comment text: Request for Trial against Decision on Refusal Patent event code: PJ02012R01D Patent event date: 19990729 Comment text: Decision to Refuse Application Patent event code: PJ02011S01I Appeal kind category: Appeal against decision to decline refusal Decision date: 19991029 Appeal identifier: 1999101003210 Request date: 19990830 |
|
| PB0901 | Examination by re-examination before a trial |
Comment text: Request for Trial against Decision on Refusal Patent event date: 19990830 Patent event code: PB09011R01I Comment text: Amendment to Specification, etc. Patent event date: 19990626 Patent event code: PB09011R02I Comment text: Amendment to Specification, etc. Patent event date: 19920711 Patent event code: PB09011R02I |
|
| B701 | Decision to grant | ||
| PB0701 | Decision of registration after re-examination before a trial |
Patent event date: 19991029 Comment text: Decision to Grant Registration Patent event code: PB07012S01D Patent event date: 19991026 Comment text: Transfer of Trial File for Re-examination before a Trial Patent event code: PB07011S01I |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 19991119 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 19991120 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20021107 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20031015 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20041011 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20051007 Start annual number: 7 End annual number: 7 |
|
| PR1001 | Payment of annual fee |
Payment date: 20061013 Start annual number: 8 End annual number: 8 |
|
| PR1001 | Payment of annual fee |
Payment date: 20071005 Start annual number: 9 End annual number: 9 |
|
| PR1001 | Payment of annual fee |
Payment date: 20081007 Start annual number: 10 End annual number: 10 |
|
| PR1001 | Payment of annual fee |
Payment date: 20091012 Start annual number: 11 End annual number: 11 |
|
| PR1001 | Payment of annual fee |
Payment date: 20101029 Start annual number: 12 End annual number: 12 |
|
| FPAY | Annual fee payment |
Payment date: 20111028 Year of fee payment: 13 |
|
| PR1001 | Payment of annual fee |
Payment date: 20111028 Start annual number: 13 End annual number: 13 |
|
| EXPY | Expiration of term | ||
| PC1801 | Expiration of term |
Termination date: 20130309 Termination category: Expiration of duration |