JP2005503358A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2005503358A5 JP2005503358A5 JP2003506646A JP2003506646A JP2005503358A5 JP 2005503358 A5 JP2005503358 A5 JP 2005503358A5 JP 2003506646 A JP2003506646 A JP 2003506646A JP 2003506646 A JP2003506646 A JP 2003506646A JP 2005503358 A5 JP2005503358 A5 JP 2005503358A5
- Authority
- JP
- Japan
- Prior art keywords
- nucleoside
- hiv
- triphosphate
- chem
- ester
- 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
- 239000002777 nucleoside Substances 0.000 description 41
- -1 2-Fluoroadenosine-5′-phosphate ester Chemical class 0.000 description 37
- 239000001226 triphosphate Substances 0.000 description 16
- 235000011178 triphosphate Nutrition 0.000 description 15
- 229910052717 sulfur Inorganic materials 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 150000003833 nucleoside derivatives Chemical class 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 10
- 230000000840 anti-viral effect Effects 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 125000003835 nucleoside group Chemical group 0.000 description 9
- 125000003729 nucleotide group Chemical group 0.000 description 9
- 241000725303 Human immunodeficiency virus Species 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 239000010452 phosphate Substances 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 238000000302 molecular modelling Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 7
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108020005196 Mitochondrial DNA Proteins 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 150000003014 phosphoric acid esters Chemical class 0.000 description 4
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000004088 simulation Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 229940104230 thymidine 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
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 101150071146 COX2 gene Proteins 0.000 description 3
- 101150086475 COXII gene Proteins 0.000 description 3
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 3
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 3
- 102100027456 Cytochrome c oxidase subunit 2 Human genes 0.000 description 3
- 101000917383 Homo sapiens Deoxycytidine kinase Proteins 0.000 description 3
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 3
- 101150021539 MT-CO2 gene Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 230000018199 S phase Effects 0.000 description 3
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 238000012925 biological evaluation Methods 0.000 description 3
- 229940095074 cyclic amp Drugs 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 2
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 description 2
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 2
- 101100512078 Caenorhabditis elegans lys-1 gene Proteins 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 108010011356 Nucleoside phosphotransferase Proteins 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 238000001190 Q-PCR Methods 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 229910005965 SO 2 Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- RZCIEJXAILMSQK-JXOAFFINSA-N TTP Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 RZCIEJXAILMSQK-JXOAFFINSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003602 anti-herpes Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000012866 crystallographic experiment Methods 0.000 description 2
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 231100001265 toxicological assessment Toxicity 0.000 description 2
- 230000032895 transmembrane transport Effects 0.000 description 2
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- HBUBKKRHXORPQB-FJFJXFQQSA-N (2R,3S,4S,5R)-2-(6-amino-2-fluoro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O HBUBKKRHXORPQB-FJFJXFQQSA-N 0.000 description 1
- IPVFGAYTKQKGBM-BYPJNBLXSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound F[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 IPVFGAYTKQKGBM-BYPJNBLXSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N 4-amino-1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical class O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 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
- JVPRTWJSEPKQGH-FDDDBJFASA-N 5-(2-bromoethoxy)-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(OCCBr)=C1 JVPRTWJSEPKQGH-FDDDBJFASA-N 0.000 description 1
- 241001388119 Anisotremus surinamensis Species 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 0 CC1C=C(*)[C@](CO*)*1 Chemical compound CC1C=C(*)[C@](CO*)*1 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000016903 DNA Polymerase gamma Human genes 0.000 description 1
- 108010014080 DNA Polymerase gamma Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010033174 Deoxycytidine kinase Proteins 0.000 description 1
- 102100029588 Deoxycytidine kinase Human genes 0.000 description 1
- 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 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- UXDDRFCJKNROTO-UHFFFAOYSA-N Glycerol 1,2-diacetate Chemical compound CC(=O)OCC(CO)OC(C)=O UXDDRFCJKNROTO-UHFFFAOYSA-N 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000001984 Multiple Symmetrical Lipomatosis Diseases 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 101100068676 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) gln-1 gene Proteins 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 1
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- CNXKXOFTMXPMTH-UAKXSSHOSA-N [1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-5-yl] hypoiodite Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(OI)=C1 CNXKXOFTMXPMTH-UAKXSSHOSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000036436 anti-hiv Effects 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
- 238000013459 approach Methods 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 208000006443 lactic acidosis Diseases 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 108091064355 mitochondrial RNA Proteins 0.000 description 1
- 230000007625 mitochondrial abnormality Effects 0.000 description 1
- 208000012268 mitochondrial disease Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 201000011171 multiple symmetric lipomatosis Diseases 0.000 description 1
- XBDUZBHKKUFFRH-UHFFFAOYSA-N n-(2-oxo-1h-pyrimidin-6-yl)benzamide Chemical compound OC1=NC=CC(NC(=O)C=2C=CC=CC=2)=N1 XBDUZBHKKUFFRH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LBQAJLBSGOBDQF-UHFFFAOYSA-N nitro azanylidynemethanesulfonate Chemical compound [O-][N+](=O)OS(=O)(=O)C#N LBQAJLBSGOBDQF-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30035601P | 2001-06-22 | 2001-06-22 | |
| US30538601P | 2001-07-13 | 2001-07-13 | |
| PCT/US2002/020245 WO2003000200A2 (en) | 2001-06-22 | 2002-06-24 | β-2'-OR 3'-HALONUCLEOSIDES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005503358A JP2005503358A (ja) | 2005-02-03 |
| JP2005503358A5 true JP2005503358A5 (https=) | 2009-11-19 |
Family
ID=26971734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003506646A Pending JP2005503358A (ja) | 2001-06-22 | 2002-06-24 | β−２’−または３’−ハロヌクレオシド |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6949522B2 (https=) |
| EP (1) | EP1478322A4 (https=) |
| JP (1) | JP2005503358A (https=) |
| KR (1) | KR20050059975A (https=) |
| CN (1) | CN100343268C (https=) |
| AU (1) | AU2002322325A1 (https=) |
| BR (1) | BR0210594A (https=) |
| CA (1) | CA2451745A1 (https=) |
| WO (1) | WO2003000200A2 (https=) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| EP1736478B1 (en) | 2000-05-26 | 2015-07-22 | IDENIX Pharmaceuticals, Inc. | Methods and compositions for treating flaviviruses and pestiviruses |
| EP2180064A3 (en) * | 2000-10-18 | 2010-08-11 | Pharmasset, Inc. | Multiplex quantification of nucleic acids in diseased cells |
| US8481712B2 (en) | 2001-01-22 | 2013-07-09 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| US7105499B2 (en) | 2001-01-22 | 2006-09-12 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
| SK286630B6 (sk) | 2001-01-22 | 2009-02-05 | Merck & Co., Inc. | Nukleozidové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
| WO2003037860A2 (en) | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| CN1678326A (zh) | 2002-06-28 | 2005-10-05 | 埃迪尼克斯(开曼)有限公司 | 用于治疗黄病毒感染的2'－c－甲基－3'－o－l－缬氨酸酯核糖呋喃基胞苷 |
| 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 |
| US7608600B2 (en) * | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| LT1576138T (lt) | 2002-11-15 | 2017-06-26 | Idenix Pharmaceuticals Llc | 2`-šakoti nukleozidai derinyje su interferonu ir flaviviridae mutacija |
| AU2003300901A1 (en) | 2002-12-12 | 2004-06-30 | Idenix (Cayman) Limited | Process for the production of 2'-branched nucleosides |
| WO2004087169A1 (en) * | 2003-03-27 | 2004-10-14 | Boehringer Ingelheim International Gmbh | Antiviral combination of nevirapine and a further antiretroviral compound |
| HUE029877T2 (en) | 2003-05-30 | 2017-04-28 | Gilead Pharmasset Llc | Modified fluorinated nucleoside analogues |
| MXPA06002997A (es) | 2003-09-18 | 2007-02-08 | Conforma Therapeutics Corp | Novedosos compuestos heterociclicos como inhibidores- hsp90. |
| JP2005289964A (ja) * | 2004-03-12 | 2005-10-20 | Ajinomoto Co Inc | ２−デオキシ−ｌ−リボース化合物の製造方法 |
| GB0505781D0 (en) * | 2005-03-21 | 2005-04-27 | Univ Cardiff | Chemical compounds |
| AU2006230447A1 (en) | 2005-03-30 | 2006-10-05 | Conforma Therapeutics Corporation | Alkynyl pyrrolopyrimidines and related analogs as HSP90-inhibitors |
| EA200800932A1 (ru) * | 2005-09-26 | 2008-10-30 | Фармассет, Инк. | Модифицированные 4`-нуклеозиды в качестве противовирусных агентов |
| ES2422290T3 (es) | 2005-12-23 | 2013-09-10 | Idenix Pharmaceuticals Inc | Procedimiento para preparar un producto intermedio sintético para la preparación de nucleósidos ramificados |
| US9296776B2 (en) * | 2007-07-09 | 2016-03-29 | Eastern Virginia Medical School | Substituted nucleoside derivatives with antiviral and antimicrobial properties |
| WO2012142093A2 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-cyano substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| EP2697242B1 (en) | 2011-04-13 | 2018-10-03 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| BR112013026345A2 (pt) | 2011-04-13 | 2019-04-24 | Merck Sharp & Dohe Corp. | composto, composição farmacêutica, uso de um composto, e, método para tratar um paciente infectado com hcv |
| US9408863B2 (en) | 2011-07-13 | 2016-08-09 | Merck Sharp & Dohme Corp. | 5′-substituted nucleoside analogs and methods of use thereof for the treatment of viral diseases |
| WO2013009735A1 (en) | 2011-07-13 | 2013-01-17 | Merck Sharp & Dohme Corp. | 5'-substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| US8673926B2 (en) | 2012-02-14 | 2014-03-18 | University Of Georgia Research Foundation, Inc. | Spiro[2.4]heptanes for treatment of flaviviridae infections |
| SG10201603288XA (en) | 2012-03-28 | 2016-05-30 | Fujifilm Corp | Salt Of 1-(2-Deoxy-2-Fluoro-4-Thio-beta-D-Arabinofuranosyl)Cytosine |
| KR20170001722A (ko) | 2012-08-13 | 2017-01-04 | 후지필름 가부시키가이샤 | 1-(2-데옥시-2-플루오로-4-티오-β-D-아라비노푸라노실)시토신의 합성 중간체, 티오뉴클레오시드의 합성 중간체, 및 그들의 제조법 |
| EP3109245B1 (en) * | 2014-02-18 | 2018-01-03 | FUJIFILM Corporation | Method for producting thiolane skeleton-type glycoconjugate, and thiolane skeleton-type glycoconjugate |
| JP6204223B2 (ja) | 2014-02-19 | 2017-09-27 | 富士フイルム株式会社 | チオピラノース化合物等の製造方法 |
| TWI678373B (zh) | 2014-10-31 | 2019-12-01 | 日商富士軟片股份有限公司 | 硫代核苷衍生物或其鹽及醫藥組合物 |
| CA3182565A1 (en) | 2015-03-06 | 2016-09-15 | Atea Pharmaceuticals, Inc. | .beta.-d-2'-deoxy-2'-.alpha.-fluoro-2'-.beta.-c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment |
| 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 |
| IL265044B2 (en) | 2016-08-31 | 2025-02-01 | Fujifilm Corp | An antitumor preparation containing the substances nab-paclitaxel and 1-(2-deoxy-2-fluoro-4-thio-D-beta-arabinofurnosyl)cytosine, a kit containing these substances and their uses |
| WO2018048937A1 (en) | 2016-09-07 | 2018-03-15 | Atea Pharmaceuticals, Inc. | 2'-substituted-n6-substituted purine nucleotides for rna virus treatment |
| IL288737B (en) | 2017-02-01 | 2022-09-01 | Atea Pharmaceuticals Inc | Hemisulfate nucleotide salt for treatment of hepatitis c virus |
| WO2019146130A1 (ja) | 2018-01-29 | 2019-08-01 | 富士フイルム株式会社 | 胆道がん用抗腫瘍剤および胆道がんの処置方法 |
| EP3773753A4 (en) | 2018-04-10 | 2021-12-22 | ATEA Pharmaceuticals, Inc. | TREATMENT OF PATIENTS INFECTED WITH THE HEPATITIS C VIRUS WITH CIRRHOSIS |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| CN115667280B (zh) * | 2020-03-25 | 2025-07-18 | 西蒙弗雷泽大学 | 一种合成核苷及其类似物的方法和试剂 |
| IL308921A (en) | 2021-06-17 | 2024-01-01 | Atea Pharmaceuticals Inc | Combination anti-HCV therapy is beneficial |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4211773A (en) | 1978-10-02 | 1980-07-08 | Sloan Kettering Institute For Cancer Research | 5-Substituted 1-(2'-Deoxy-2'-substituted-β-D-arabinofuranosyl)pyrimidine nucleosides |
| US4625020A (en) | 1983-11-18 | 1986-11-25 | Bristol-Myers Company | Nucleoside process |
| US4666892A (en) | 1984-03-06 | 1987-05-19 | Sloan-Kettering Memorial Cancer Center | Method and composition for hepatitis treatment with pyrimidine nucleoside compounds |
| US4681933A (en) | 1986-05-01 | 1987-07-21 | University Of Georgia Research Foundation, Inc. | 2',3'-dideoxy-5-substituted uridines and related compounds as antiviral agents |
| US5446029A (en) * | 1986-07-04 | 1995-08-29 | Medivir Ab | Anti-retroviral activity of 2',3'-dideoxy-3'-fluoronucleosides |
| DD279407A1 (de) * | 1986-07-24 | 1990-06-06 | Akad Wissenschaften Ddr | Verfahren zur herstellung eines mittels gegen aids |
| US5215970A (en) * | 1987-04-16 | 1993-06-01 | Medivir Ab | Nucleosides and nucleotide analogues, pharmaceutical composition and processes for the preparation of the compounds |
| DE3715666A1 (de) | 1987-05-11 | 1988-11-24 | Kodak Ag | Kassettenentlade- und beladegeraet |
| GB8712115D0 (en) | 1987-05-22 | 1987-06-24 | Hoffmann La Roche | Pyrimidine derivatives |
| US5246924A (en) | 1987-09-03 | 1993-09-21 | Sloan-Kettering Institute For Cancer Research | Method for treating hepatitis B virus infections using 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil |
| GB8726136D0 (en) * | 1987-11-07 | 1987-12-09 | Wellcome Found | Therapeutic nucleosides |
| US4908440A (en) | 1987-11-12 | 1990-03-13 | Bristol Myers Company | 2',3'-dideoxy-2'-fluoroarabinopyrimidine nucleosides |
| SE8802173D0 (sv) | 1988-06-10 | 1988-06-10 | Astra Ab | Pyrimidine derivatives |
| SE8802687D0 (sv) | 1988-07-20 | 1988-07-20 | Astra Ab | Nucleoside derivatives |
| US5034518A (en) | 1989-05-23 | 1991-07-23 | Southern Research Institute | 2-fluoro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl) adenine nucleosides |
| 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 |
| US5128458A (en) | 1990-04-20 | 1992-07-07 | Southern Research Institute | 2',3'-dideoxy-4'-thioribonucleosides as antiviral agents |
| EP0463470A3 (en) | 1990-06-22 | 1992-08-05 | F. Hoffmann-La Roche Ag | Process for the preparation of a fluorotetrahydrofuranone derivative |
| JPH0477485A (ja) * | 1990-07-19 | 1992-03-11 | Yamasa Shoyu Co Ltd | ２’，３’―ジデヒドロ―２’，３’―ジデオキシウリジン誘導体およびその製造法 |
| US5817799A (en) | 1990-07-23 | 1998-10-06 | The United States Of America As Represented By The Department Of Health And Human Services | 2'-Fluorofuranosyl derivatives and methods for preparing 2'-fluoropyrimidine and 2'-fluoropurine nucleosides |
| IT1246983B (it) | 1990-11-13 | 1994-12-12 | Consiglio Nazionale Ricerche | L-2'-desossiuridine e composizioni farmaceutiche che le contengono. |
| GB9200150D0 (en) * | 1992-01-06 | 1992-02-26 | Wellcome Found | Therapeutic nucleosides |
| DE69324244T2 (de) * | 1992-01-06 | 1999-09-30 | The Wellcome Foundation Ltd., Greenford | Therapeutische nukleoside der 2',3'-dideoxy-3'-fluor -purin reihe |
| US5426183A (en) | 1992-06-22 | 1995-06-20 | Eli Lilly And Company | Catalytic stereoselective glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| EP0626970A1 (en) | 1992-12-18 | 1994-12-07 | The University Of Alberta | Dihydropyrimidine nucleosides with antiviral properties |
| US5424416A (en) | 1993-08-25 | 1995-06-13 | Eli Lilly And Company | Process for preparation of 2-deoxy-2,2-difluoro-D-ribofuranosyl-3,5-hydroxy protected-1-alkyl and aryl sulfonates and their use in preparation of 2',2'-difluoro-2'-deoxy nucleosides |
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| 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 |
| US6355790B1 (en) * | 1997-06-03 | 2002-03-12 | University Of Rochester | Inhibition of HIV replication using a mutated transfer RNA primer |
| WO1999043691A1 (en) | 1998-02-25 | 1999-09-02 | Emory University | 2'-fluoronucleosides |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| EP1736478B1 (en) | 2000-05-26 | 2015-07-22 | IDENIX Pharmaceuticals, Inc. | Methods and compositions for treating flaviviruses and pestiviruses |
-
2002
- 2002-06-24 EP EP02756310A patent/EP1478322A4/en not_active Withdrawn
- 2002-06-24 WO PCT/US2002/020245 patent/WO2003000200A2/en not_active Ceased
- 2002-06-24 CA CA002451745A patent/CA2451745A1/en not_active Abandoned
- 2002-06-24 JP JP2003506646A patent/JP2005503358A/ja active Pending
- 2002-06-24 BR BR0210594-2A patent/BR0210594A/pt not_active IP Right Cessation
- 2002-06-24 CN CNB028164555A patent/CN100343268C/zh not_active Expired - Fee Related
- 2002-06-24 AU AU2002322325A patent/AU2002322325A1/en not_active Abandoned
- 2002-06-24 US US10/179,612 patent/US6949522B2/en not_active Expired - Fee Related
- 2002-06-24 KR KR1020037016775A patent/KR20050059975A/ko not_active Ceased
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2005503358A5 (https=) | ||
| US6949522B2 (en) | β-2′- or 3′-halonucleosides | |
| US8895531B2 (en) | 2′-fluoronucleoside phosphonates as antiviral agents | |
| Mahmoud et al. | Antiviral nucleoside and nucleotide analogs: a review | |
| KR100634342B1 (ko) | B형 간염의 치료용 β-L-2'-데옥시-뉴클레오시드 | |
| US4963662A (en) | Fluorinated nucleosides and method for treating retrovirus infections therewith | |
| JP2002504558A (ja) | ２’−フルオロヌクレオシド | |
| MX2013013570A (es) | Profarmacos de monofosfato de purina para el tratamiento de infecciones virales. | |
| KR20110115601A (ko) | 암 및 바이러스 감염 치료용 퓨린 뉴클레오시드 모노포스페이트 프로드럭 | |
| JP2011246469A (ja) | Ｂ型肝炎ウイルス活性を持ったヌクレオシド | |
| AU768059B2 (en) | Beta-L-2'-deoxy-nucleosides for the treatment of HIV infection | |
| ES2261072B1 (es) | Fosforotioatos derivados de analogos a nucleosido para terapia antirretroviral. | |
| AU2003261475B2 (en) | Beta-L-2'-deoxy-nucleosides for the treatment of HIV infection | |
| KR100886653B1 (ko) | 2'-플루오로뉴클레오사이드 | |
| TW201210602A (en) | Phosphorus-containing prodrugs and their therapeutic use | |
| HK1036069B (en) | Nucleosides with anti-hepatitis b virus activity |