EA011720B1 - ПРОИЗВОДНЫЕ β-D-НУКЛЕОЗИДА И ИХ ПРИМЕНЕНИЕ - Google Patents
ПРОИЗВОДНЫЕ β-D-НУКЛЕОЗИДА И ИХ ПРИМЕНЕНИЕ Download PDFInfo
- Publication number
- EA011720B1 EA011720B1 EA200600582A EA200600582A EA011720B1 EA 011720 B1 EA011720 B1 EA 011720B1 EA 200600582 A EA200600582 A EA 200600582A EA 200600582 A EA200600582 A EA 200600582A EA 011720 B1 EA011720 B1 EA 011720B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- acetyl
- triphosphate
- diphosphate
- monophosphate
- cyclopropyl
- Prior art date
Links
- -1 β-D NUCLEOSIDE DERIVATIVES Chemical class 0.000 title description 314
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 33
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 32
- 239000010452 phosphate Substances 0.000 claims abstract description 32
- 150000002148 esters Chemical class 0.000 claims abstract description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 8
- 239000000460 chlorine Substances 0.000 claims abstract description 8
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000011630 iodine Substances 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 238000011282 treatment Methods 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 31
- 229940079593 drug Drugs 0.000 claims description 25
- 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 19
- 108010050904 Interferons Proteins 0.000 claims description 18
- 102000014150 Interferons Human genes 0.000 claims description 18
- 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 18
- 229960000329 ribavirin Drugs 0.000 claims description 18
- 229940079322 interferon Drugs 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 208000005176 Hepatitis C Diseases 0.000 claims description 15
- 241000711549 Hepacivirus C Species 0.000 claims description 14
- 241000700605 Viruses Species 0.000 claims description 14
- 239000002552 dosage form Substances 0.000 claims description 10
- 239000003443 antiviral agent Substances 0.000 claims description 9
- 150000003548 thiazolidines Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 208000010710 hepatitis C virus infection Diseases 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 712
- 150000004712 monophosphates Chemical class 0.000 description 537
- 229940104302 cytosine Drugs 0.000 description 361
- 239000001226 triphosphate Substances 0.000 description 359
- 235000011178 triphosphate Nutrition 0.000 description 359
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 359
- 239000001177 diphosphate Substances 0.000 description 358
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 358
- 235000011180 diphosphates Nutrition 0.000 description 358
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 104
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 96
- 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 94
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 93
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 78
- 239000002777 nucleoside Substances 0.000 description 78
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 77
- 125000000217 alkyl group Chemical group 0.000 description 75
- 229930024421 Adenine Natural products 0.000 description 67
- 229960000643 adenine Drugs 0.000 description 67
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 64
- 238000000034 method Methods 0.000 description 62
- QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 0.000 description 55
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 52
- 235000000346 sugar Nutrition 0.000 description 49
- 229940035893 uracil Drugs 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 46
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 45
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 45
- 239000002585 base Substances 0.000 description 45
- 229960002949 fluorouracil Drugs 0.000 description 45
- 125000003835 nucleoside group Chemical group 0.000 description 43
- 230000000694 effects Effects 0.000 description 40
- 125000002252 acyl group Chemical group 0.000 description 35
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 31
- 150000003833 nucleoside derivatives Chemical class 0.000 description 31
- 239000003112 inhibitor Substances 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 24
- 208000000143 urethritis Diseases 0.000 description 24
- 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 23
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- 208000015181 infectious disease Diseases 0.000 description 22
- KPYHRMNYOUGKKI-UHFFFAOYSA-N phosphoric acid;1h-pyrimidine-2,4-dione Chemical compound OP(O)(O)=O.O=C1C=CNC(=O)N1 KPYHRMNYOUGKKI-UHFFFAOYSA-N 0.000 description 22
- 235000021317 phosphate Nutrition 0.000 description 21
- 229940002612 prodrug Drugs 0.000 description 21
- 239000000651 prodrug Substances 0.000 description 21
- 239000002342 ribonucleoside Substances 0.000 description 21
- 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 20
- 150000002632 lipids Chemical class 0.000 description 20
- 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
- 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 18
- 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 18
- 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 17
- 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 17
- 210000004027 cell Anatomy 0.000 description 17
- DDIYWLKNBSUXJC-UHFFFAOYSA-N cyclopropyl phosphono hydrogen phosphate Chemical compound C1CC1OP(=O)(O)OP(=O)(O)O DDIYWLKNBSUXJC-UHFFFAOYSA-N 0.000 description 17
- 241000282693 Cercopithecidae Species 0.000 description 16
- 125000003729 nucleotide group Chemical group 0.000 description 16
- 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 15
- 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 15
- 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 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000006722 reduction reaction Methods 0.000 description 15
- 108091005804 Peptidases Proteins 0.000 description 14
- 102000035195 Peptidases Human genes 0.000 description 14
- 101150016222 SNAT1 gene Proteins 0.000 description 14
- LIPOUNRJVLNBCD-UHFFFAOYSA-N acetyl dihydrogen phosphate Chemical compound CC(=O)OP(O)(O)=O LIPOUNRJVLNBCD-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 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 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- UXBXOCZWFRBBBW-UHFFFAOYSA-N cyclopropyl dihydrogen phosphate Chemical compound OP(O)(=O)OC1CC1 UXBXOCZWFRBBBW-UHFFFAOYSA-N 0.000 description 13
- 239000004365 Protease Substances 0.000 description 12
- 229960001456 adenosine triphosphate Drugs 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 12
- 238000010511 deprotection reaction Methods 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- MRZDHXLJHIMNOR-UHFFFAOYSA-N 8-fluoro-7h-purin-6-amine Chemical compound NC1=NC=NC2=C1NC(F)=N2 MRZDHXLJHIMNOR-UHFFFAOYSA-N 0.000 description 11
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 11
- CMYSVPKNZOINDP-UHFFFAOYSA-N acetyl diphosphate Chemical compound CC(=O)OP(O)(=O)OP(O)(O)=O CMYSVPKNZOINDP-UHFFFAOYSA-N 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
- XYJPXPIPUZKEEX-UHFFFAOYSA-N phosphoric acid;1h-pyrimidine-2,4-dione Chemical compound OP(O)(O)=O.OP(O)(O)=O.O=C1C=CNC(=O)N1 XYJPXPIPUZKEEX-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- MKZUDFZKTZOCRS-UHFFFAOYSA-N diphosphono hydrogen phosphate;1h-pyrimidine-2,4-dione Chemical compound O=C1C=CNC(=O)N1.OP(O)(=O)OP(O)(=O)OP(O)(O)=O MKZUDFZKTZOCRS-UHFFFAOYSA-N 0.000 description 10
- VJWZESGAMZOMQV-UHFFFAOYSA-N diphosphono hydrogen phosphate;5-fluoro-1h-pyrimidine-2,4-dione Chemical compound FC1=CNC(=O)NC1=O.OP(O)(=O)OP(O)(=O)OP(O)(O)=O VJWZESGAMZOMQV-UHFFFAOYSA-N 0.000 description 10
- RAYIFMWTQKNDNK-UHFFFAOYSA-N phosphono dihydrogen phosphate;1h-pyrimidine-2,4-dione Chemical compound O=C1C=CNC(=O)N1.OP(O)(=O)OP(O)(O)=O RAYIFMWTQKNDNK-UHFFFAOYSA-N 0.000 description 10
- 235000019419 proteases Nutrition 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 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 9
- WKMPTBDYDNUJLF-UHFFFAOYSA-N 2-fluoroadenine Chemical compound NC1=NC(F)=NC2=C1N=CN2 WKMPTBDYDNUJLF-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 125000003342 alkenyl group Chemical group 0.000 description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 9
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 8
- COMQOWNKGHJXFS-UHFFFAOYSA-N 2,8-difluoro-7h-purin-6-amine Chemical compound NC1=NC(F)=NC2=C1NC(F)=N2 COMQOWNKGHJXFS-UHFFFAOYSA-N 0.000 description 8
- CDKQXPWHBOXGGT-UHFFFAOYSA-N 2-amino-8-fluoro-1,7-dihydropurin-6-one phosphono dihydrogen phosphate Chemical compound OP(O)(=O)OP(O)(O)=O.Nc1nc2nc(F)[nH]c2c(=O)[nH]1 CDKQXPWHBOXGGT-UHFFFAOYSA-N 0.000 description 8
- WOWWMFFWXXWORS-UHFFFAOYSA-N 8-fluoro-7H-purin-6-amine phosphoric acid Chemical compound OP(O)(O)=O.Nc1ncnc2nc(F)[nH]c12 WOWWMFFWXXWORS-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- RPANQMMNHQTKBM-UHFFFAOYSA-N Nc1nc2nc(F)[nH]c2c(=O)[nH]1.OP(O)(=O)OP(O)(=O)OP(O)(O)=O Chemical compound Nc1nc2nc(F)[nH]c2c(=O)[nH]1.OP(O)(=O)OP(O)(=O)OP(O)(O)=O RPANQMMNHQTKBM-UHFFFAOYSA-N 0.000 description 8
- FUCCBBMGMYAMQP-UHFFFAOYSA-N Nc1ncnc2nc(F)[nH]c12.OP(O)(=O)OP(O)(=O)OP(O)(O)=O Chemical compound Nc1ncnc2nc(F)[nH]c12.OP(O)(=O)OP(O)(=O)OP(O)(O)=O FUCCBBMGMYAMQP-UHFFFAOYSA-N 0.000 description 8
- RRJXANLJQZRXSH-UHFFFAOYSA-N OP(O)(=O)OP(O)(O)=O.Nc1nc(F)nc2nc(F)[nH]c12 Chemical compound OP(O)(=O)OP(O)(O)=O.Nc1nc(F)nc2nc(F)[nH]c12 RRJXANLJQZRXSH-UHFFFAOYSA-N 0.000 description 8
- QMSSRZLWQUMIDJ-UHFFFAOYSA-N OP(O)(=O)OP(O)(O)=O.Nc1nc(F)nc2nc[nH]c12 Chemical compound OP(O)(=O)OP(O)(O)=O.Nc1nc(F)nc2nc[nH]c12 QMSSRZLWQUMIDJ-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 125000001246 bromo group Chemical group Br* 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 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 8
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 8
- LBCAJGROHPKKMJ-UHFFFAOYSA-N diphosphono hydrogen phosphate 2-fluoro-7H-purin-6-amine Chemical compound Nc1nc(F)nc2nc[nH]c12.OP(O)(=O)OP(O)(=O)OP(O)(O)=O LBCAJGROHPKKMJ-UHFFFAOYSA-N 0.000 description 8
- 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
- 238000007429 general method Methods 0.000 description 8
- 239000007800 oxidant agent Substances 0.000 description 8
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- ZHTWWICNKGBOAV-UHFFFAOYSA-N 2,8-difluoro-7H-purin-6-amine phosphoric acid Chemical compound OP(O)(O)=O.Nc1nc(F)nc2nc(F)[nH]c12 ZHTWWICNKGBOAV-UHFFFAOYSA-N 0.000 description 7
- LCUOZFPWQUJXOL-UHFFFAOYSA-N 2-amino-8-fluoro-1,7-dihydropurin-6-one phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(O)=O.Nc1nc2nc(F)[nH]c2c(=O)[nH]1 LCUOZFPWQUJXOL-UHFFFAOYSA-N 0.000 description 7
- AMZMZRBFNJFVAR-UHFFFAOYSA-N 2-fluoro-7H-purin-6-amine phosphoric acid Chemical compound OP(O)(O)=O.OP(O)(O)=O.Nc1nc(F)nc2nc[nH]c12 AMZMZRBFNJFVAR-UHFFFAOYSA-N 0.000 description 7
- PHPXRBAYZYFBEV-UHFFFAOYSA-N 8-fluoro-7H-purin-6-amine phosphono dihydrogen phosphate Chemical compound OP(O)(=O)OP(O)(O)=O.Nc1ncnc2nc(F)[nH]c12 PHPXRBAYZYFBEV-UHFFFAOYSA-N 0.000 description 7
- HHWHNCUAAIWMQL-UHFFFAOYSA-N Nc1nc(F)nc2nc(F)[nH]c12.OP(O)(=O)OP(O)(=O)OP(O)(O)=O Chemical compound Nc1nc(F)nc2nc(F)[nH]c12.OP(O)(=O)OP(O)(=O)OP(O)(O)=O HHWHNCUAAIWMQL-UHFFFAOYSA-N 0.000 description 7
- JAOGHMPJXCCOEJ-UHFFFAOYSA-N OP(O)(O)=O.Nc1nc(F)nc2nc[nH]c12 Chemical compound OP(O)(O)=O.Nc1nc(F)nc2nc[nH]c12 JAOGHMPJXCCOEJ-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- 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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- 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
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- 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
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- 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
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- A61K31/7072—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 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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