CZ301182B6 - Použití nukleosidových derivátu pro výrobu farmaceutických prostredku pro lécení infekcí vyvolaných flaviviry a pestiviry - Google Patents
Použití nukleosidových derivátu pro výrobu farmaceutických prostredku pro lécení infekcí vyvolaných flaviviry a pestiviry Download PDFInfo
- Publication number
- CZ301182B6 CZ301182B6 CZ20024225A CZ20024225A CZ301182B6 CZ 301182 B6 CZ301182 B6 CZ 301182B6 CZ 20024225 A CZ20024225 A CZ 20024225A CZ 20024225 A CZ20024225 A CZ 20024225A CZ 301182 B6 CZ301182 B6 CZ 301182B6
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- CZ
- Czechia
- Prior art keywords
- alkyl
- hydrogen
- group
- pharmaceutically acceptable
- compound
- Prior art date
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- 241000710778 Pestivirus Species 0.000 title claims abstract description 35
- 241000710831 Flavivirus Species 0.000 title claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
- 150000003833 nucleoside derivatives Chemical class 0.000 title abstract description 22
- 208000015181 infectious disease Diseases 0.000 title abstract description 9
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 357
- -1 5-azacytidinyl Chemical group 0.000 claims description 234
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 204
- 229910052739 hydrogen Inorganic materials 0.000 claims description 203
- 239000001257 hydrogen Substances 0.000 claims description 201
- 150000001875 compounds Chemical class 0.000 claims description 174
- 125000002252 acyl group Chemical group 0.000 claims description 156
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 137
- 229940104302 cytosine Drugs 0.000 claims description 102
- 150000003839 salts Chemical class 0.000 claims description 99
- 229910019142 PO4 Inorganic materials 0.000 claims description 86
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 85
- 239000010452 phosphate Substances 0.000 claims description 85
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 83
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 76
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 65
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 64
- 150000002431 hydrogen Chemical class 0.000 claims description 63
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 229910052760 oxygen Inorganic materials 0.000 claims description 57
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 56
- 125000000304 alkynyl group Chemical group 0.000 claims description 54
- 229920002554 vinyl polymer Polymers 0.000 claims description 51
- 229960000643 adenine Drugs 0.000 claims description 50
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 49
- 229930024421 Adenine Natural products 0.000 claims description 48
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 48
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
- 229910004013 NO 2 Inorganic materials 0.000 claims description 43
- 229910052717 sulfur Inorganic materials 0.000 claims description 39
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 38
- 229940113082 thymine Drugs 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 23
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 18
- 150000002148 esters Chemical class 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 12
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 10
- 229960000329 ribavirin Drugs 0.000 claims description 10
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 150000003548 thiazolidines Chemical class 0.000 claims description 8
- 102000014150 Interferons Human genes 0.000 claims description 7
- 108010050904 Interferons Proteins 0.000 claims description 7
- 229940079322 interferon Drugs 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 6
- 229940035893 uracil Drugs 0.000 claims description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 4
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 4
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims description 3
- MGAXHFMCFLLMNG-UHFFFAOYSA-N 1h-pyrimidine-6-thione Chemical compound SC1=CC=NC=N1 MGAXHFMCFLLMNG-UHFFFAOYSA-N 0.000 claims description 3
- SVXNJCYYMRMXNM-UHFFFAOYSA-N 5-amino-2h-1,2,4-triazin-3-one Chemical compound NC=1C=NNC(=O)N=1 SVXNJCYYMRMXNM-UHFFFAOYSA-N 0.000 claims description 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 3
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 claims description 3
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 claims description 3
- 229960004413 flucytosine Drugs 0.000 claims description 3
- HBCQSNAFLVXVAY-UHFFFAOYSA-N pyrimidine-2-thiol Chemical compound SC1=NC=CC=N1 HBCQSNAFLVXVAY-UHFFFAOYSA-N 0.000 claims description 3
- PVRBGBGMDLPYKG-UHFFFAOYSA-N 6-benzyl-7h-purine Chemical compound N=1C=NC=2N=CNC=2C=1CC1=CC=CC=C1 PVRBGBGMDLPYKG-UHFFFAOYSA-N 0.000 claims description 2
- DBCMWACNZJYUHS-UHFFFAOYSA-N 6-ethenyl-7h-purine Chemical compound C=CC1=NC=NC2=C1NC=N2 DBCMWACNZJYUHS-UHFFFAOYSA-N 0.000 claims description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000006725 C1-C10 alkenyl group Chemical group 0.000 claims 1
- 230000003441 anti-flavivirus Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 18
- 230000002265 prevention Effects 0.000 abstract description 7
- 239000000460 chlorine Substances 0.000 description 311
- 150000004712 monophosphates Chemical class 0.000 description 245
- 239000001226 triphosphate Substances 0.000 description 205
- 235000011178 triphosphate Nutrition 0.000 description 205
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 204
- 239000001177 diphosphate Substances 0.000 description 180
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 180
- 235000011180 diphosphates Nutrition 0.000 description 180
- 239000002585 base Substances 0.000 description 127
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 88
- 229910052801 chlorine Inorganic materials 0.000 description 86
- 235000021317 phosphate Nutrition 0.000 description 85
- 229910052794 bromium Inorganic materials 0.000 description 82
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 82
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 80
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 76
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 76
- 125000003282 alkyl amino group Chemical group 0.000 description 69
- 239000002777 nucleoside Substances 0.000 description 69
- 229940002612 prodrug Drugs 0.000 description 69
- 239000000651 prodrug Substances 0.000 description 69
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 65
- 125000003342 alkenyl group Chemical group 0.000 description 63
- 125000003118 aryl group Chemical group 0.000 description 54
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 54
- 239000002243 precursor Substances 0.000 description 54
- 229910052731 fluorine Inorganic materials 0.000 description 52
- 239000011737 fluorine Substances 0.000 description 52
- 150000002632 lipids Chemical group 0.000 description 52
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 48
- 108090000765 processed proteins & peptides Proteins 0.000 description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 44
- 125000001424 substituent group Chemical group 0.000 description 44
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 42
- 150000001720 carbohydrates Chemical class 0.000 description 41
- 235000012000 cholesterol Nutrition 0.000 description 41
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 41
- DEMJYWYZJFNNNB-UHFFFAOYSA-N OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O Chemical compound OP(O)(O)=O.OP(O)(O)=O.OP(O)(O)=O DEMJYWYZJFNNNB-UHFFFAOYSA-N 0.000 description 40
- 125000000539 amino acid group Chemical group 0.000 description 40
- 235000014633 carbohydrates Nutrition 0.000 description 40
- 238000001727 in vivo Methods 0.000 description 40
- 229910005965 SO 2 Inorganic materials 0.000 description 39
- 125000003835 nucleoside group Chemical group 0.000 description 39
- 235000000346 sugar Nutrition 0.000 description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 35
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 32
- 150000003904 phospholipids Chemical class 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 31
- QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 0.000 description 28
- 125000006239 protecting group Chemical group 0.000 description 28
- WYVPBFVWZCTMPP-UHFFFAOYSA-N OP(O)(=O)OP(=O)(O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)OP(=O)(O)O Chemical compound OP(O)(=O)OP(=O)(O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)OP(=O)(O)O WYVPBFVWZCTMPP-UHFFFAOYSA-N 0.000 description 23
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 22
- CSSIWXFUZVBFND-UHFFFAOYSA-N OP(O)(=O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)O Chemical compound OP(O)(=O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)O CSSIWXFUZVBFND-UHFFFAOYSA-N 0.000 description 22
- 229910052740 iodine Inorganic materials 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- 230000009467 reduction Effects 0.000 description 20
- 238000006722 reduction reaction Methods 0.000 description 20
- 239000000126 substance Substances 0.000 description 20
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 17
- 230000000840 anti-viral effect Effects 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
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- 241000700605 Viruses Species 0.000 description 14
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- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 13
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 12
- 239000002342 ribonucleoside Substances 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 10
- 239000003443 antiviral agent Substances 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 208000005176 Hepatitis C Diseases 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
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- RDMGMZAMWLSHNS-UHFFFAOYSA-N 3,7-dihydropurin-6-one;phosphoric acid Chemical compound OP(O)(O)=O.O=C1NC=NC2=C1NC=N2 RDMGMZAMWLSHNS-UHFFFAOYSA-N 0.000 description 8
- ZKLKXUYJIUGECX-UHFFFAOYSA-N 5-methyl-1h-pyrimidine-2,4-dione;phosphoric acid Chemical compound OP(O)(O)=O.CC1=CNC(=O)NC1=O ZKLKXUYJIUGECX-UHFFFAOYSA-N 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
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- 210000004027 cell Anatomy 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
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- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
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- 150000008163 sugars Chemical class 0.000 description 8
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 8
- GBSSBTKECSBHSE-UHFFFAOYSA-N 2-amino-8-fluoro-3,7-dihydropurin-6-one Chemical compound O=C1NC(N)=NC2=C1NC(F)=N2 GBSSBTKECSBHSE-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
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- DDIYWLKNBSUXJC-UHFFFAOYSA-N cyclopropyl phosphono hydrogen phosphate Chemical compound C1CC1OP(=O)(O)OP(=O)(O)O DDIYWLKNBSUXJC-UHFFFAOYSA-N 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- LFGGWVMUILESJS-UHFFFAOYSA-N 1,7-dihydropurin-6-one phosphono dihydrogen phosphate Chemical compound OP(O)(=O)OP(=O)(O)O.N1C=NC=2N=CNC2C1=O LFGGWVMUILESJS-UHFFFAOYSA-N 0.000 description 6
- BALXSYQWXWVVJJ-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;phosphoric acid Chemical compound OP(O)(O)=O.O=C1NC(N)=NC2=C1NC=N2 BALXSYQWXWVVJJ-UHFFFAOYSA-N 0.000 description 6
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- ZKKBWNOSVZIFNJ-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;diphosphono hydrogen phosphate Chemical compound O=C1NC(N)=NC2=C1NC=N2.OP(O)(=O)OP(O)(=O)OP(O)(O)=O ZKKBWNOSVZIFNJ-UHFFFAOYSA-N 0.000 description 5
- JWDLEVZYUTZUBA-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;phosphono dihydrogen phosphate Chemical compound OP(O)(=O)OP(O)(O)=O.O=C1NC(N)=NC2=C1NC=N2 JWDLEVZYUTZUBA-UHFFFAOYSA-N 0.000 description 5
- GOGWHNRWODMUNB-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(O)=O.N1C(N)=NC(=O)C2=C1N=CN2 GOGWHNRWODMUNB-UHFFFAOYSA-N 0.000 description 5
- AHASLLQCJNEMQG-UHFFFAOYSA-N 5-methyl-1h-pyrimidine-2,4-dione;phosphono dihydrogen phosphate Chemical compound CC1=CNC(=O)NC1=O.OP(O)(=O)OP(O)(O)=O AHASLLQCJNEMQG-UHFFFAOYSA-N 0.000 description 5
- MRZDHXLJHIMNOR-UHFFFAOYSA-N 8-fluoro-7h-purin-6-amine Chemical compound NC1=NC=NC2=C1NC(F)=N2 MRZDHXLJHIMNOR-UHFFFAOYSA-N 0.000 description 5
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 5
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229960001456 adenosine triphosphate Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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Applications Claiming Priority (2)
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|---|---|---|---|
| US20767400P | 2000-05-26 | 2000-05-26 | |
| US28327601P | 2001-04-11 | 2001-04-11 |
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| CZ20024225A3 CZ20024225A3 (cs) | 2003-10-15 |
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| CZ20024225A CZ301182B6 (cs) | 2000-05-26 | 2001-05-23 | Použití nukleosidových derivátu pro výrobu farmaceutických prostredku pro lécení infekcí vyvolaných flaviviry a pestiviry |
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| CN100387237C (zh) * | 1998-08-10 | 2008-05-14 | 艾丹尼克斯(开曼)有限公司 | 用于治疗乙型肝炎的β-L-2'-脱氧-核苷 |
| US6444652B1 (en) * | 1998-08-10 | 2002-09-03 | Novirio Pharmaceuticals Limited | β-L-2'-deoxy-nucleosides for the treatment of hepatitis B |
| US20020056123A1 (en) * | 2000-03-09 | 2002-05-09 | Gad Liwerant | Sharing a streaming video |
| PY0111577A (es) * | 2000-05-23 | 2017-01-02 | Idenix Cayman Ltd | Métodos y composiciones para el tratamiento del virus de la hepatitis c |
| AP2006003708A0 (en) | 2000-05-26 | 2006-08-31 | Idenix Cayman Ltd | Methods and compositions for treating flavivirusesand pestiviruses |
| JP2004533406A (ja) * | 2000-10-18 | 2004-11-04 | フアーマセツト・リミテツド | ウイルス感染症および異常細胞増殖を治療するための修飾ヌクレオシド |
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| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20010523 |