CZ301169B6 - Použití nukleosidového derivátu pro výrobu léciva pro lécení hepatitidy C - Google Patents
Použití nukleosidového derivátu pro výrobu léciva pro lécení hepatitidy C Download PDFInfo
- Publication number
- CZ301169B6 CZ301169B6 CZ20024149A CZ20024149A CZ301169B6 CZ 301169 B6 CZ301169 B6 CZ 301169B6 CZ 20024149 A CZ20024149 A CZ 20024149A CZ 20024149 A CZ20024149 A CZ 20024149A CZ 301169 B6 CZ301169 B6 CZ 301169B6
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- CZ
- Czechia
- Prior art keywords
- acetyl
- alkyl
- triphosphate
- diphosphate
- monophosphate
- Prior art date
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- 238000011282 treatment Methods 0.000 title claims abstract description 47
- 150000003833 nucleoside derivatives Chemical class 0.000 title claims abstract description 38
- 239000003814 drug Substances 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 208000005176 Hepatitis C Diseases 0.000 title description 17
- 241000711549 Hepacivirus C Species 0.000 claims abstract description 84
- 230000002265 prevention Effects 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 516
- -1 5-halouracil Chemical compound 0.000 claims description 324
- 229940104302 cytosine Drugs 0.000 claims description 258
- 229910052757 nitrogen Inorganic materials 0.000 claims description 144
- 125000000217 alkyl group Chemical group 0.000 claims description 139
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 96
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 90
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 89
- 150000001875 compounds Chemical class 0.000 claims description 87
- 229910052739 hydrogen Inorganic materials 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 70
- 229930024421 Adenine Natural products 0.000 claims description 62
- 229960000643 adenine Drugs 0.000 claims description 62
- 125000002252 acyl group Chemical group 0.000 claims description 59
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 57
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 49
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 48
- 229940113082 thymine Drugs 0.000 claims description 48
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 239000002243 precursor Substances 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 35
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 229910019142 PO4 Inorganic materials 0.000 claims description 25
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 24
- 239000010452 phosphate Substances 0.000 claims description 24
- 229920002554 vinyl polymer Polymers 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 102000014150 Interferons Human genes 0.000 claims description 20
- 108010050904 Interferons Proteins 0.000 claims description 20
- 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 18
- 229910004013 NO 2 Inorganic materials 0.000 claims description 17
- 229940079322 interferon Drugs 0.000 claims description 17
- 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 17
- 229960000329 ribavirin Drugs 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 16
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 6
- 229940035893 uracil Drugs 0.000 claims description 6
- 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
- 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 3
- DBCMWACNZJYUHS-UHFFFAOYSA-N 6-ethenyl-7h-purine Chemical compound C=CC1=NC=NC2=C1NC=N2 DBCMWACNZJYUHS-UHFFFAOYSA-N 0.000 claims description 3
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-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
- FVLAYJRLBLHIPV-UHFFFAOYSA-N pyrimidin-5-amine Chemical compound NC1=CN=CN=C1 FVLAYJRLBLHIPV-UHFFFAOYSA-N 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
- NPYPQKXJJZZSAX-UHFFFAOYSA-N 5-benzylpyrimidine Chemical class C=1N=CN=CC=1CC1=CC=CC=C1 NPYPQKXJJZZSAX-UHFFFAOYSA-N 0.000 claims description 2
- NOYDQGFVFOQSAJ-UHFFFAOYSA-N 5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=CN=C1 NOYDQGFVFOQSAJ-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
- COTYNDRSENVEFI-UHFFFAOYSA-N 1-pyrimidin-5-ylethanone Chemical compound CC(=O)C1=CN=CN=C1 COTYNDRSENVEFI-UHFFFAOYSA-N 0.000 claims 1
- 150000005697 5-halopyrimidines Chemical class 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 claims 1
- 150000007979 thiazole derivatives Chemical class 0.000 claims 1
- 230000000840 anti-viral effect Effects 0.000 abstract description 18
- 208000010710 hepatitis C virus infection Diseases 0.000 abstract description 5
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 150000004712 monophosphates Chemical class 0.000 description 516
- 239000000460 chlorine Substances 0.000 description 450
- 239000001177 diphosphate Substances 0.000 description 343
- 235000011180 diphosphates Nutrition 0.000 description 343
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 342
- 239000001226 triphosphate Substances 0.000 description 324
- 235000011178 triphosphate Nutrition 0.000 description 323
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 322
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 125
- 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 98
- 239000002585 base Substances 0.000 description 82
- 239000002777 nucleoside Substances 0.000 description 81
- QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 0.000 description 54
- 235000000346 sugar Nutrition 0.000 description 49
- 125000003835 nucleoside group Chemical group 0.000 description 47
- 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 46
- 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 39
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 34
- 238000003786 synthesis reaction Methods 0.000 description 32
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 31
- 229910052801 chlorine Inorganic materials 0.000 description 31
- 229960002949 fluorouracil Drugs 0.000 description 31
- 229910052794 bromium Inorganic materials 0.000 description 29
- 125000006239 protecting group Chemical group 0.000 description 28
- 238000000034 method Methods 0.000 description 27
- 125000003282 alkyl amino group Chemical group 0.000 description 26
- 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 25
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 25
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 24
- 239000003112 inhibitor Substances 0.000 description 23
- 235000021317 phosphate Nutrition 0.000 description 23
- 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 22
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 22
- 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 22
- 239000000126 substance Substances 0.000 description 22
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 21
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 21
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 20
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 150000002431 hydrogen Chemical class 0.000 description 20
- 125000000304 alkynyl group Chemical group 0.000 description 19
- 125000003118 aryl group Chemical group 0.000 description 19
- 150000008163 sugars Chemical class 0.000 description 19
- 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 18
- 208000015181 infectious disease Diseases 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- YONPFOKPAKAQLX-UHFFFAOYSA-N 5-fluoro-1h-pyrimidine-2,4-dione;phosphoric acid Chemical compound OP(O)(O)=O.FC1=CNC(=O)NC1=O YONPFOKPAKAQLX-UHFFFAOYSA-N 0.000 description 16
- 229910052731 fluorine Inorganic materials 0.000 description 16
- 239000011737 fluorine Substances 0.000 description 16
- 150000002632 lipids Chemical group 0.000 description 16
- 125000001424 substituent group Chemical group 0.000 description 16
- 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 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- VQRWLYMKQQBDFK-UHFFFAOYSA-N diphosphono hydrogen phosphate;5-methyl-1h-pyrimidine-2,4-dione Chemical compound CC1=CNC(=O)NC1=O.OP(O)(=O)OP(O)(=O)OP(O)(O)=O VQRWLYMKQQBDFK-UHFFFAOYSA-N 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 230000009467 reduction Effects 0.000 description 15
- 238000006722 reduction reaction Methods 0.000 description 15
- 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 14
- 125000003729 nucleotide group Chemical group 0.000 description 14
- HXERRKOZCLQLFP-UHFFFAOYSA-N 1,7-dihydropurin-6-one diphosphono hydrogen phosphate Chemical compound OP(O)(=O)OP(=O)(O)OP(=O)(O)O.N1C=NC=2N=CNC2C1=O HXERRKOZCLQLFP-UHFFFAOYSA-N 0.000 description 13
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 13
- 239000002342 ribonucleoside Substances 0.000 description 13
- 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 12
- HDWCXVUQUHKLHD-UHFFFAOYSA-N OP(O)(=O)OP(O)(O)=O.Fc1c[nH]c(=O)[nH]c1=O Chemical compound OP(O)(=O)OP(O)(O)=O.Fc1c[nH]c(=O)[nH]c1=O HDWCXVUQUHKLHD-UHFFFAOYSA-N 0.000 description 12
- 125000000539 amino acid group Chemical group 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- 150000001720 carbohydrates Chemical class 0.000 description 12
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 12
- 150000003904 phospholipids Chemical class 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
- 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 11
- 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 11
- MRZDHXLJHIMNOR-UHFFFAOYSA-N 8-fluoro-7h-purin-6-amine Chemical compound NC1=NC=NC2=C1NC(F)=N2 MRZDHXLJHIMNOR-UHFFFAOYSA-N 0.000 description 11
- GKPKKAAZTQERJY-UHFFFAOYSA-N P(=O)(O)(O)O.P(=O)(O)(O)O.N1C=NC=2N=CNC2C1=O Chemical compound P(=O)(O)(O)O.P(=O)(O)(O)O.N1C=NC=2N=CNC2C1=O GKPKKAAZTQERJY-UHFFFAOYSA-N 0.000 description 11
- 229910005965 SO 2 Inorganic materials 0.000 description 11
- 241000700605 Viruses Species 0.000 description 11
- ACPOSOLRSSPDDC-UHFFFAOYSA-N [hydroxy-[hydroxy(phosphonooxy)phosphoryl]oxyphosphoryl] acetate Chemical compound CC(=O)OP(=O)(O)OP(=O)(O)OP(=O)(O)O ACPOSOLRSSPDDC-UHFFFAOYSA-N 0.000 description 11
- LIPOUNRJVLNBCD-UHFFFAOYSA-N acetyl dihydrogen phosphate Chemical compound CC(=O)OP(O)(O)=O LIPOUNRJVLNBCD-UHFFFAOYSA-N 0.000 description 11
- 235000014633 carbohydrates Nutrition 0.000 description 11
- 235000012000 cholesterol Nutrition 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
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- CMYSVPKNZOINDP-UHFFFAOYSA-N acetyl diphosphate Chemical compound CC(=O)OP(O)(=O)OP(O)(O)=O CMYSVPKNZOINDP-UHFFFAOYSA-N 0.000 description 10
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 10
- UXBXOCZWFRBBBW-UHFFFAOYSA-N cyclopropyl dihydrogen phosphate Chemical compound OP(O)(=O)OC1CC1 UXBXOCZWFRBBBW-UHFFFAOYSA-N 0.000 description 10
- DDIYWLKNBSUXJC-UHFFFAOYSA-N cyclopropyl phosphono hydrogen phosphate Chemical compound C1CC1OP(=O)(O)OP(=O)(O)O DDIYWLKNBSUXJC-UHFFFAOYSA-N 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
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- WKMPTBDYDNUJLF-UHFFFAOYSA-N 2-fluoroadenine Chemical compound NC1=NC(F)=NC2=C1N=CN2 WKMPTBDYDNUJLF-UHFFFAOYSA-N 0.000 description 9
- LABDSBNMRCTNEK-UHFFFAOYSA-N 5-methyl-1h-pyrimidine-2,4-dione;phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(O)=O.CC1=CNC(=O)NC1=O LABDSBNMRCTNEK-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 9
- 239000003443 antiviral agent Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- ZWBMVHLPYUKGKY-UHFFFAOYSA-N cyclopropyl [hydroxy(phosphonooxy)phosphoryl] hydrogen phosphate Chemical compound C1CC1OP(=O)(O)OP(=O)(O)OP(=O)(O)O ZWBMVHLPYUKGKY-UHFFFAOYSA-N 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 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 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 8
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 239000007800 oxidant agent Substances 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
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
- A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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