JP2005519916A - ウィルス感染治療用n4−アシルシトシンヌクレオシド類 - Google Patents
ウィルス感染治療用n4−アシルシトシンヌクレオシド類 Download PDFInfo
- Publication number
- JP2005519916A JP2005519916A JP2003563467A JP2003563467A JP2005519916A JP 2005519916 A JP2005519916 A JP 2005519916A JP 2003563467 A JP2003563467 A JP 2003563467A JP 2003563467 A JP2003563467 A JP 2003563467A JP 2005519916 A JP2005519916 A JP 2005519916A
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- fluorine
- dideoxy
- compound
- pharmaceutically acceptable
- 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.)
- Pending
Links
- 208000036142 Viral infection Diseases 0.000 title abstract description 4
- 230000009385 viral infection Effects 0.000 title abstract description 4
- 239000002777 nucleoside Substances 0.000 title description 25
- 125000003835 nucleoside group Chemical group 0.000 title description 8
- 229940002612 prodrug Drugs 0.000 claims abstract description 338
- 239000000651 prodrug Substances 0.000 claims abstract description 338
- 150000003839 salts Chemical class 0.000 claims abstract description 324
- 238000000034 method Methods 0.000 claims abstract description 29
- 208000015181 infectious disease Diseases 0.000 claims abstract description 22
- STRZQWQNZQMHQR-UAKXSSHOSA-N 5-fluorocytidine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 STRZQWQNZQMHQR-UAKXSSHOSA-N 0.000 claims abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 931
- 239000001257 hydrogen Substances 0.000 claims description 929
- 150000001875 compounds Chemical class 0.000 claims description 694
- 229910052731 fluorine Inorganic materials 0.000 claims description 660
- -1 phosphate ester Chemical group 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000003342 alkenyl group Chemical group 0.000 claims description 74
- 125000000304 alkynyl group Chemical group 0.000 claims description 74
- 125000003118 aryl group Chemical group 0.000 claims description 68
- 125000001188 haloalkyl group Chemical group 0.000 claims description 50
- 229910052794 bromium Inorganic materials 0.000 claims description 46
- 229910052801 chlorine Inorganic materials 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 46
- 150000002367 halogens Chemical class 0.000 claims description 45
- 229910052740 iodine Inorganic materials 0.000 claims description 45
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 39
- 125000004001 thioalkyl group Chemical group 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 229910019142 PO4 Inorganic materials 0.000 claims description 24
- 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 claims description 24
- 239000010452 phosphate Substances 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
- 238000001727 in vivo Methods 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 235000012000 cholesterol Nutrition 0.000 claims description 12
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 12
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 7
- BDVFEQPECMQQEK-OBNKUBODSA-N 6-amino-6-(4-bromobenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2C=CC(Br)=CC=2)NC(=O)N1[C@@H]1O[C@H](CO)C=C1 BDVFEQPECMQQEK-OBNKUBODSA-N 0.000 claims description 5
- ZZOWHGNRJBACEC-OBNKUBODSA-N 6-amino-6-(4-bromobenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2C=CC(Br)=CC=2)NC(=O)N1[C@H]1CC[C@@H](CO)O1 ZZOWHGNRJBACEC-OBNKUBODSA-N 0.000 claims description 5
- VCLLXLWPTDLADT-OBNKUBODSA-N 6-amino-6-(4-chlorobenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2C=CC(Cl)=CC=2)NC(=O)N1[C@@H]1O[C@H](CO)C=C1 VCLLXLWPTDLADT-OBNKUBODSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- LYHLJDQNKUSXKT-OBNKUBODSA-N 6-amino-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-6-(4-iodobenzoyl)-1H-pyrimidin-2-one Chemical compound IC1=CC=C(C(=O)C2(NC(N([C@H]3C=C[C@@H](CO)O3)C=C2F)=O)N)C=C1 LYHLJDQNKUSXKT-OBNKUBODSA-N 0.000 claims description 4
- XPZKEBBLAZUJAS-OBNKUBODSA-N 6-amino-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-6-(4-iodobenzoyl)-1H-pyrimidin-2-one Chemical compound IC1=CC=C(C(=O)C2(NC(N([C@H]3CC[C@@H](CO)O3)C=C2F)=O)N)C=C1 XPZKEBBLAZUJAS-OBNKUBODSA-N 0.000 claims description 4
- DJVMNMGZLLNCOX-OBNKUBODSA-N 6-amino-5-fluoro-6-(4-fluorobenzoyl)-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2C=CC(F)=CC=2)NC(=O)N1[C@H]1CC[C@@H](CO)O1 DJVMNMGZLLNCOX-OBNKUBODSA-N 0.000 claims description 4
- VIVHUVPGOGXJLT-POXCNRTASA-N 6-amino-6-(4-ethylbenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C1=CC(CC)=CC=C1C(=O)C1(N)C(F)=CN([C@H]2C=C[C@@H](CO)O2)C(=O)N1 VIVHUVPGOGXJLT-POXCNRTASA-N 0.000 claims description 4
- GYKMBBKSGZJFDI-POXCNRTASA-N 6-amino-6-(4-ethylbenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=CC(CC)=CC=C1C(=O)C1(N)C(F)=CN([C@@H]2O[C@H](CO)CC2)C(=O)N1 GYKMBBKSGZJFDI-POXCNRTASA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- VPNFLKVIAZECPH-OBNKUBODSA-N 6-amino-5-fluoro-6-(4-fluorobenzoyl)-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound FC1=CC=C(C(=O)C2(NC(N([C@H]3C=C[C@@H](CO)O3)C=C2F)=O)N)C=C1 VPNFLKVIAZECPH-OBNKUBODSA-N 0.000 claims description 2
- 238000010276 construction Methods 0.000 claims 26
- 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 claims 13
- 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 claims 13
- 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 claims 10
- QFZSFOGFWZZUNY-OBNKUBODSA-N 6-amino-6-(4-chlorobenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound ClC1=CC=C(C(=O)C2(NC(N([C@H]3CC[C@@H](CO)O3)C=C2F)=O)N)C=C1 QFZSFOGFWZZUNY-OBNKUBODSA-N 0.000 claims 4
- XLZMFYOWVOAWEJ-DBMQZSJKSA-N 6-amino-6-(4-tert-butylbenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)C1(N)C(F)=CN([C@H]2C=C[C@@H](CO)O2)C(=O)N1 XLZMFYOWVOAWEJ-DBMQZSJKSA-N 0.000 claims 2
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 claims 2
- 229940124411 anti-hiv antiviral agent Drugs 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- WLVNAHXIMSQHMW-OCDMVOQQSA-N 6-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(4-ethylbenzoyl)-5-fluoro-1H-pyrimidin-2-one Chemical compound C(C)C1=CC=C(C(=O)C2(NC(N([C@H]3[C@H](O)[C@H](O)[C@@H](CO)O3)C=C2F)=O)N)C=C1 WLVNAHXIMSQHMW-OCDMVOQQSA-N 0.000 claims 1
- LJTXIDHLSJRCRI-JYCRYNECSA-N 6-amino-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-6-(4-methoxybenzoyl)-1H-pyrimidin-2-one Chemical compound C1=CC(OC)=CC=C1C(=O)C1(N)C(F)=CN([C@H]2C=C[C@@H](CO)O2)C(=O)N1 LJTXIDHLSJRCRI-JYCRYNECSA-N 0.000 claims 1
- ORAFXVZDHPCYMY-QQDBQQHDSA-N 6-amino-6-(1-benzothiophene-2-carbonyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2SC3=CC=CC=C3C=2)NC(=O)N1[C@H]1CC[C@@H](CO)O1 ORAFXVZDHPCYMY-QQDBQQHDSA-N 0.000 claims 1
- BSSDTTPDXHUFRY-OBNKUBODSA-N 6-amino-6-(3-bromobenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2C=C(Br)C=CC=2)NC(=O)N1[C@H]1CC[C@@H](CO)O1 BSSDTTPDXHUFRY-OBNKUBODSA-N 0.000 claims 1
- DMEDABDOQFXXBC-OBNKUBODSA-N 6-amino-6-(3-chlorobenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C=2C=C(Cl)C=CC=2)NC(=O)N1[C@H]1CC[C@@H](CO)O1 DMEDABDOQFXXBC-OBNKUBODSA-N 0.000 claims 1
- NOIZCHKDVXBABB-DBMQZSJKSA-N 6-amino-6-(4-tert-butylbenzoyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)C1(N)C(F)=CN([C@@H]2O[C@H](CO)CC2)C(=O)N1 NOIZCHKDVXBABB-DBMQZSJKSA-N 0.000 claims 1
- YLCCKDTVZYPNME-OBNKUBODSA-N 6-amino-6-(cyclohexanecarbonyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C2CCCCC2)NC(=O)N1[C@@H]1O[C@H](CO)C=C1 YLCCKDTVZYPNME-OBNKUBODSA-N 0.000 claims 1
- AMHSVLOKQVVFRS-OBNKUBODSA-N 6-amino-6-(cyclohexanecarbonyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-1H-pyrimidin-2-one Chemical compound C1(CCCCC1)C(=O)C1(NC(N([C@H]2CC[C@@H](CO)O2)C=C1F)=O)N AMHSVLOKQVVFRS-OBNKUBODSA-N 0.000 claims 1
- WLQFNOGTGWAMFV-QFZKOWMDSA-N 6-amino-6-(cyclopentanecarbonyl)-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C1=C(F)C(N)(C(=O)C2CCCC2)NC(=O)N1[C@@H]1O[C@H](CO)C=C1 WLQFNOGTGWAMFV-QFZKOWMDSA-N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 125000004401 m-toluyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C(*)=O 0.000 claims 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
- 241000700721 Hepatitis B virus Species 0.000 abstract description 34
- 241000725303 Human immunodeficiency virus Species 0.000 abstract description 24
- 239000000203 mixture Substances 0.000 abstract description 20
- 241001465754 Metazoa Species 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 916
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 612
- 239000011737 fluorine Substances 0.000 description 612
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 311
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 21
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 14
- 239000001226 triphosphate Substances 0.000 description 13
- 235000011178 triphosphate Nutrition 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 11
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 11
- 239000001177 diphosphate Substances 0.000 description 11
- 235000011180 diphosphates Nutrition 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- 150000003904 phospholipids Chemical class 0.000 description 11
- 150000003014 phosphoric acid esters Chemical class 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 125000001544 thienyl group Chemical group 0.000 description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 229940104302 cytosine Drugs 0.000 description 9
- WQDLCTMKSKFSAT-GPTJOGTASA-N (3r,5s)-5-[[tert-butyl(diphenyl)silyl]-hydroxymethyl]-3-phenylselanyloxolan-2-one Chemical compound [Se]([C@@H]1C[C@H](OC1=O)C(O)[Si](C(C)(C)C)(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 WQDLCTMKSKFSAT-GPTJOGTASA-N 0.000 description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
- 208000031886 HIV Infections Diseases 0.000 description 7
- 208000037357 HIV infectious disease Diseases 0.000 description 7
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000002541 furyl group Chemical group 0.000 description 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 6
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 125000001624 naphthyl group Chemical group 0.000 description 6
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 208000030507 AIDS Diseases 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 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 4
- XSSYCIGJYCVRRK-RQJHMYQMSA-N (-)-carbovir Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1C[C@H](CO)C=C1 XSSYCIGJYCVRRK-RQJHMYQMSA-N 0.000 description 3
- WREGKURFCTUGRC-UHFFFAOYSA-N 4-Amino-1-[5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1C1OC(CO)CC1 WREGKURFCTUGRC-UHFFFAOYSA-N 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Natural products NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 229960002555 zidovudine Drugs 0.000 description 3
- HSBKFSPNDWWPSL-CAHLUQPWSA-N 4-amino-5-fluoro-1-[(2r,5s)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1C=C[C@@H](CO)O1 HSBKFSPNDWWPSL-CAHLUQPWSA-N 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 206010019759 Hepatitis chronic persistent Diseases 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- GBBJCSTXCAQSSJ-XQXXSGGOSA-N clevudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1[C@H](F)[C@@H](O)[C@H](CO)O1 GBBJCSTXCAQSSJ-XQXXSGGOSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- FZYYPNOHKXTKLI-NTSWFWBYSA-N 2-amino-9-[(2r,5s)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)C=C1 FZYYPNOHKXTKLI-NTSWFWBYSA-N 0.000 description 1
- AOYDTYAJSZPRLO-VJBFUYBPSA-N 4-amino-1-[(2S,5R)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one 2-phosphonoacetic acid phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O.OC(=O)CP(O)(O)=O.O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)SC1 AOYDTYAJSZPRLO-VJBFUYBPSA-N 0.000 description 1
- WZGBNAXNHRMYLG-ZXFLCMHBSA-N 4-amino-1-[(2r,4r,5s)-4,5-bis(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical class O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](CO)C1 WZGBNAXNHRMYLG-ZXFLCMHBSA-N 0.000 description 1
- JTEGQNOMFQHVDC-RQJHMYQMSA-N 4-amino-1-[(2s,5r)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)SC1 JTEGQNOMFQHVDC-RQJHMYQMSA-N 0.000 description 1
- QBEIABZPRBJOFU-CAHLUQPWSA-N 4-amino-5-fluoro-1-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)CC1 QBEIABZPRBJOFU-CAHLUQPWSA-N 0.000 description 1
- POQLJGALHYBUQV-GZALTDKGSA-N 6-acetyl-6-amino-5-fluoro-3-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-1H-pyrimidin-2-one Chemical compound C(C)(=O)C1(NC(N([C@H]2C=C[C@@H](CO)O2)C=C1F)=O)N POQLJGALHYBUQV-GZALTDKGSA-N 0.000 description 1
- 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 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229940124602 FDA-approved drug Drugs 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 229960004748 abacavir Drugs 0.000 description 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- YGZQYMMFALYKCO-GXTWGEPZSA-N n-[1-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)N=C(NC(=O)C=2C=CC=CC=2)C=C1 YGZQYMMFALYKCO-GXTWGEPZSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000523 zalcitabine Drugs 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- C07H19/06—Pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34155501P | 2001-12-14 | 2001-12-14 | |
| PCT/US2002/040081 WO2003063771A2 (en) | 2001-12-14 | 2002-12-13 | N4-acylcytosine nucleosides for treatment of viral iinfections |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005519916A true JP2005519916A (ja) | 2005-07-07 |
| JP2005519916A5 JP2005519916A5 (enExample) | 2010-03-18 |
Family
ID=23338072
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003563467A Pending JP2005519916A (ja) | 2001-12-14 | 2002-12-13 | ウィルス感染治療用n4−アシルシトシンヌクレオシド類 |
Country Status (10)
| Country | Link |
|---|---|
| US (6) | US7105527B2 (enExample) |
| EP (1) | EP1569652A4 (enExample) |
| JP (1) | JP2005519916A (enExample) |
| KR (1) | KR100978904B1 (enExample) |
| CN (1) | CN100560073C (enExample) |
| AU (2) | AU2002365234B2 (enExample) |
| BR (1) | BR0214944A (enExample) |
| CA (1) | CA2470255C (enExample) |
| MX (1) | MXPA04005779A (enExample) |
| WO (2) | WO2003063771A2 (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6790228B2 (en) * | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
| KR100974917B1 (ko) | 2000-04-13 | 2010-08-09 | 파마셋 인코포레이티드 | 간염 바이러스 감염 치료를 위한 3'- 또는2'-하이드록시메틸 치환된 뉴클레오시드 유도체 |
| MY164523A (en) * | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| AU2001272923A1 (en) | 2000-05-26 | 2001-12-11 | Idenix (Cayman) Limited | Methods and compositions for treating flaviviruses and pestiviruses |
| CN100560073C (zh) * | 2001-12-14 | 2009-11-18 | 法玛塞特公司 | 用于治疗病毒感染的n4-酰基胞嘧啶核苷 |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| NZ537662A (en) | 2002-06-28 | 2007-10-26 | Idenix Cayman Ltd | 2'-C-methyl-3'-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| KR20050035194A (ko) * | 2002-06-28 | 2005-04-15 | 이데닉스 (케이만) 리미티드 | 플라비비리다에 감염 치료용 2'-c-메틸-3'-o-l-발린에스테르 리보푸라노실 사이티딘 |
| WO2004013300A2 (en) | 2002-08-01 | 2004-02-12 | Pharmasset Inc. | Compounds with the bicyclo[4.2.1]nonane system for the treatment of flaviviridae infections |
| CN1849142A (zh) * | 2002-11-15 | 2006-10-18 | 埃迪尼克斯(开曼)有限公司 | 2′-支链核苷和黄病毒突变 |
| KR20050109918A (ko) | 2002-12-12 | 2005-11-22 | 이데닉스 (케이만) 리미티드 | 2'-분지형 뉴클레오시드의 제조 방법 |
| CA2425031A1 (en) * | 2003-04-01 | 2004-10-01 | Smithkline Beecham Corporation | Pharmaceutical compositions |
| KR100883703B1 (ko) * | 2003-05-30 | 2009-02-12 | 파마셋 인코포레이티드 | 변형 불소화 뉴클레오시드 유사체 |
| WO2005097618A2 (en) * | 2004-04-01 | 2005-10-20 | Achillion Pharmaceuticals, Inc. | Low dose therapy for treating viral infections |
| CN101023094B (zh) * | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
| EP3109244B1 (en) | 2004-09-14 | 2019-03-06 | Gilead Pharmasset LLC | Preparation of 2'fluoro-2'-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
| EP1802315A2 (en) * | 2004-10-19 | 2007-07-04 | Achillion Pharmaceuticals, Inc. | Combination therapy for treating viral infections |
| US7968703B2 (en) * | 2005-03-07 | 2011-06-28 | Shire Canada Inc. | Process and methods for the preparation of optically active cis-2-hydroxymethyl-4- (cytosin-1'-yl)-1,3-oxathiolane or pharmaceutically acceptable salts thereof |
| WO2007075876A2 (en) * | 2005-12-23 | 2007-07-05 | Idenix Pharmaceuticals, Inc. | Process for preparing a synthetic intermediate for preparation of branched nucleosides |
| GB0623493D0 (en) | 2006-11-24 | 2007-01-03 | Univ Cardiff | Chemical compounds |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| MX2011006891A (es) | 2008-12-23 | 2011-10-06 | Pharmasset Inc | Fosforamidatos de nucleosidos. |
| US8716263B2 (en) | 2008-12-23 | 2014-05-06 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| CN102753563A (zh) | 2008-12-23 | 2012-10-24 | 吉利德制药有限责任公司 | 核苷类似物 |
| TWI583692B (zh) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| EA026341B9 (ru) | 2010-03-31 | 2021-12-27 | ГАЙЛИД ФАРМАССЕТ ЭлЭлСи | Кристаллическая форма нуклеозидфосфорамидата |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
| US8841275B2 (en) | 2010-11-30 | 2014-09-23 | Gilead Pharmasset Llc | 2′-spiro-nucleosides and derivatives thereof useful for treating hepatitis C virus and dengue virus infections |
| EP2709613B2 (en) | 2011-09-16 | 2020-08-12 | Gilead Pharmasset LLC | Methods for treating hcv |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| CN103242400B (zh) * | 2012-02-08 | 2016-06-08 | 河南师范大学 | 具有抗hiv活性的5-取代嘧啶核苷-噻唑啉酮杂化体及其制备方法 |
| UA118256C2 (uk) | 2013-01-31 | 2018-12-26 | Гіліад Фармассет Елелсі | Комбінований склад двох противірусних сполук |
| EP3650014B1 (en) | 2013-08-27 | 2021-10-06 | Gilead Pharmasset LLC | Combination formulation of two antiviral compounds |
| CN107427530B (zh) | 2015-03-06 | 2020-09-08 | 阿堤亚制药公司 | 用于HCV治疗的β-D-2’-脱氧-2’α-氟-2’-β-C-取代的-2-改性的-N6-取代的嘌呤核苷酸 |
| WO2018013937A1 (en) | 2016-07-14 | 2018-01-18 | Atea Pharmaceuticals, Inc. | Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| AU2017324939B2 (en) | 2016-09-07 | 2021-10-14 | Atea Pharmaceuticals, Inc. | 2'-substituted-N6-substituted purine nucleotides for RNA virus treatment |
| US10519186B2 (en) | 2017-02-01 | 2019-12-31 | Atea Pharmaceuticals, Inc. | Nucleotide hemi-sulfate salt for the treatment of hepatitis C virus |
| KR20200140865A (ko) | 2018-04-10 | 2020-12-16 | 아테아 파마슈티컬즈, 인크. | 간경변증을 갖는 hcv 감염 환자의 치료 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| CN117500494A (zh) | 2021-06-17 | 2024-02-02 | 阿堤亚制药公司 | 有利的抗hcv联合疗法 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US13660A (en) * | 1855-10-09 | Improvements | ||
| US3309359A (en) * | 1965-10-22 | 1967-03-14 | Hoffmann La Roche | N-mono-acyl-5-fluorocytosine derivatives and process |
| NL8202626A (nl) | 1982-06-29 | 1984-01-16 | Stichting Rega V Z W | Derivaten van 9-(2-hydroxyethoxymethyl)guanine. |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| GB8719367D0 (en) | 1987-08-15 | 1987-09-23 | Wellcome Found | Therapeutic compounds |
| ZA886890B (en) * | 1987-10-09 | 1989-05-30 | Hoffmann La Roche | Novel dideoxycytidine derivatives |
| US6350753B1 (en) * | 1988-04-11 | 2002-02-26 | Biochem Pharma Inc. | 2-Substituted-4-substituted-1,3-dioxolanes and use thereof |
| NL8901258A (nl) | 1989-05-19 | 1990-12-17 | Stichting Rega V Z W | 5-halogeno-2',3'-dideoxycytidinederivaten in geneesmiddelen voor het behandelen van retrovirus-infecties. |
| DD293498A5 (de) | 1989-07-20 | 1991-09-05 | Zi Fuer Molekularbiologie Der Adw,De | Verfahren zur herstellung eines mittels fuer die behandlung oder prophylaxe von hepatits-infektionen bei mensch und tier |
| JPH05310777A (ja) | 1992-05-14 | 1993-11-22 | Yoshitomi Pharmaceut Ind Ltd | 2’−デオキシ−2’−メチリデンシチジン化合物 |
| TW254946B (enExample) * | 1992-12-18 | 1995-08-21 | Hoffmann La Roche | |
| TW374087B (en) | 1993-05-25 | 1999-11-11 | Univ Yale | L-2',3'-dideoxy nucleotide analogs as anti-hepatitis B(HBV) and anti-HIV agents |
| TW574214B (en) | 1994-06-08 | 2004-02-01 | Pfizer | Corticotropin releasing factor antagonists |
| 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 |
| GB9525606D0 (en) * | 1995-12-14 | 1996-02-14 | Iaf Biochem Int | Method and compositions for the synthesis of dioxolane nucleosides with - configuration |
| WO1998017281A1 (en) * | 1996-10-24 | 1998-04-30 | Vion Pharmaceuticals, Inc. | MONOPHOSPHATE PRODRUGS OF β-L-FD4C AND β-L-FddC AS POTENT ANTIVIRAL AGENTS |
| CA2311581A1 (en) * | 1997-11-25 | 1999-06-03 | Protarga, Inc. | Nucleoside analog compositions and uses thereof |
| US6348587B1 (en) | 1998-02-25 | 2002-02-19 | Emory University | 2′-Fluoronucleosides |
| CA2425359A1 (en) * | 2000-10-13 | 2002-04-18 | Shire Biochem Inc. | Dioxolane analogs for improved inter-cellular delivery |
| EP1411954B1 (en) * | 2000-10-18 | 2010-12-15 | Pharmasset, Inc. | Modified nucleosides for treatment of viral infections and abnormal cellular proliferation |
| CN100560073C (zh) * | 2001-12-14 | 2009-11-18 | 法玛塞特公司 | 用于治疗病毒感染的n4-酰基胞嘧啶核苷 |
-
2002
- 2002-12-13 CN CNB028278402A patent/CN100560073C/zh not_active Expired - Fee Related
- 2002-12-13 CA CA2470255A patent/CA2470255C/en not_active Expired - Fee Related
- 2002-12-13 BR BR0214944-3A patent/BR0214944A/pt not_active Application Discontinuation
- 2002-12-13 WO PCT/US2002/040081 patent/WO2003063771A2/en not_active Ceased
- 2002-12-13 AU AU2002365234A patent/AU2002365234B2/en not_active Ceased
- 2002-12-13 KR KR1020047009263A patent/KR100978904B1/ko not_active Expired - Fee Related
- 2002-12-13 EP EP02804833A patent/EP1569652A4/en not_active Withdrawn
- 2002-12-13 JP JP2003563467A patent/JP2005519916A/ja active Pending
- 2002-12-13 MX MXPA04005779A patent/MXPA04005779A/es active IP Right Grant
- 2002-12-13 US US10/318,511 patent/US7105527B2/en not_active Expired - Fee Related
- 2002-12-16 AU AU2002364730A patent/AU2002364730A1/en not_active Abandoned
- 2002-12-16 US US10/320,350 patent/US6908924B2/en not_active Ceased
- 2002-12-16 WO PCT/US2002/040090 patent/WO2003051306A2/en not_active Ceased
-
2006
- 2006-07-31 US US11/461,338 patent/US20070078080A1/en not_active Abandoned
-
2007
- 2007-06-21 US US11/821,076 patent/USRE42015E1/en not_active Expired - Fee Related
-
2008
- 2008-01-04 US US11/969,427 patent/US8114997B2/en not_active Expired - Fee Related
-
2012
- 2012-02-13 US US13/371,654 patent/US20120202766A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN100560073C (zh) | 2009-11-18 |
| KR20040094398A (ko) | 2004-11-09 |
| WO2003063771A3 (en) | 2005-07-07 |
| US20090176730A1 (en) | 2009-07-09 |
| MXPA04005779A (es) | 2005-05-16 |
| WO2003051306A2 (en) | 2003-06-26 |
| AU2002364730A8 (en) | 2003-06-30 |
| WO2003063771A2 (en) | 2003-08-07 |
| US20030176319A1 (en) | 2003-09-18 |
| US8114997B2 (en) | 2012-02-14 |
| CA2470255C (en) | 2012-01-17 |
| BR0214944A (pt) | 2005-06-07 |
| US20070078080A1 (en) | 2007-04-05 |
| KR100978904B1 (ko) | 2010-08-31 |
| USRE42015E1 (en) | 2010-12-28 |
| AU2002365234B2 (en) | 2009-01-29 |
| AU2002364730A1 (en) | 2003-06-30 |
| EP1569652A2 (en) | 2005-09-07 |
| CA2470255A1 (en) | 2003-08-07 |
| US6908924B2 (en) | 2005-06-21 |
| US20040214844A1 (en) | 2004-10-28 |
| US20120202766A1 (en) | 2012-08-09 |
| EP1569652A4 (en) | 2008-07-02 |
| WO2003051306A3 (en) | 2003-12-18 |
| CN1617726A (zh) | 2005-05-18 |
| US7105527B2 (en) | 2006-09-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8114997B2 (en) | N4-acylcytosine nucleosides for treatment of viral infections | |
| AU2002365234A1 (en) | N4-acylcytosine nucleosides for treatment of viral infections | |
| EP0637315B1 (en) | Adenosine derivatives having a2 agonist activity | |
| EP3150600B1 (en) | Dihydropyrimido loop derivative as hbv inhibitor | |
| WO2014135107A1 (zh) | 新的核苷氨基磷酸酯化合物及其应用 | |
| JP2020525442A (ja) | 合成のための化合物、組成物、及び方法 | |
| CN103687866A (zh) | 用于治疗病毒性感染的嘌呤单磷酸酯前药 | |
| CN104231023B (zh) | 三环稠杂环类核苷氨基磷酸酯化合物、其制备方法及应用 | |
| JP2016531153A (ja) | 3−アリール−5−置換イソキノリン−1−オン化合物及びその治療的使用 | |
| TW201605885A (zh) | 尿嘧啶核苷酸類似物及其製備方法和應用 | |
| AU2005286329A1 (en) | DNA-PK inhibitors | |
| EA036892B1 (ru) | Макрогетероциклические нуклеозидные производные и их аналоги, получение и применение | |
| US20030162992A1 (en) | Preparation of intermediates useful in the synthesis of antiviral nucleosides | |
| Koszytkowska-Stawińska et al. | Synthesis of aza-analogues of Ganciclovir | |
| WO2025098545A1 (en) | Nucleoside derivatives as antiviral agents against coronaviruses | |
| WO2021031997A1 (zh) | 二氢嘧啶衍生物及其用途 | |
| HK1234054B (zh) | 作为hbv抑制剂的二氢嘧啶并环衍生物 | |
| JPWO2018110591A1 (ja) | 抗ウイルス活性を有する2’−デオキシ−7−デアザプリンヌクレオシド誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20051209 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090728 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091023 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091030 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091124 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091201 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20100127 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100223 |