KR100279953B1 - 항-b형 간염 바이러스제 및 항-사람 면역결핍 바이러스제로서의 l-2',3'-디데옥시 누클레오시드 유사체 - Google Patents
항-b형 간염 바이러스제 및 항-사람 면역결핍 바이러스제로서의 l-2',3'-디데옥시 누클레오시드 유사체 Download PDFInfo
- Publication number
- KR100279953B1 KR100279953B1 KR1019950705353A KR19950705353A KR100279953B1 KR 100279953 B1 KR100279953 B1 KR 100279953B1 KR 1019950705353 A KR1019950705353 A KR 1019950705353A KR 19950705353 A KR19950705353 A KR 19950705353A KR 100279953 B1 KR100279953 B1 KR 100279953B1
- Authority
- KR
- South Korea
- Prior art keywords
- dideoxy
- beta
- virus
- compound
- compound according
- 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.)
- Expired - Lifetime
Links
- 239000002777 nucleoside Substances 0.000 title claims description 35
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 title abstract description 13
- 150000003833 nucleoside derivatives Chemical class 0.000 title description 16
- 208000002672 hepatitis B Diseases 0.000 title description 8
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 154
- 241000700721 Hepatitis B virus Species 0.000 claims abstract description 56
- 230000010076 replication Effects 0.000 claims abstract description 27
- 230000002401 inhibitory effect Effects 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 33
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 25
- -1 nucleoside compound Chemical class 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 14
- 239000000654 additive Substances 0.000 claims description 5
- 239000006186 oral dosage form Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000006201 parenteral dosage form Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 39
- 241000700605 Viruses Species 0.000 abstract description 28
- 229940124411 anti-hiv antiviral agent Drugs 0.000 abstract description 10
- 229960004413 flucytosine Drugs 0.000 abstract description 9
- 231100000053 low toxicity Toxicity 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 8
- 230000005764 inhibitory process Effects 0.000 abstract description 8
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 abstract description 7
- 241001430294 unidentified retrovirus Species 0.000 abstract description 5
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 238000000034 method Methods 0.000 description 63
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 34
- QBEIABZPRBJOFU-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-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-VDTYLAMSSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 238000011282 treatment Methods 0.000 description 27
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 22
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 20
- 239000003814 drug Substances 0.000 description 20
- 208000015181 infectious disease Diseases 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 17
- 229940104302 cytosine Drugs 0.000 description 17
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 208000031886 HIV Infections Diseases 0.000 description 14
- 230000036436 anti-hiv Effects 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 12
- 208000037357 HIV infectious disease Diseases 0.000 description 11
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 108020005196 Mitochondrial DNA Proteins 0.000 description 10
- 208000036142 Viral infection Diseases 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 230000009385 viral infection Effects 0.000 description 10
- 208000030507 AIDS Diseases 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229940029575 guanosine Drugs 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- WREGKURFCTUGRC-SVRRBLITSA-N 4-amino-1-[(2s,5r)-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)CC1 WREGKURFCTUGRC-SVRRBLITSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000969 carrier Substances 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 229940035893 uracil Drugs 0.000 description 7
- OIRDTQYFTABQOQ-DEGSGYPDSA-N (2S,3S,4R,5S)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound [C@H]1([C@@H](O)[C@@H](O)[C@@H](O1)CO)N1C2=NC=NC(=C2N=C1)N OIRDTQYFTABQOQ-DEGSGYPDSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 6
- 230000000840 anti-viral effect Effects 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 150000004702 methyl esters Chemical class 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 229940113082 thymine Drugs 0.000 description 6
- 230000029812 viral genome replication Effects 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 102100034343 Integrase Human genes 0.000 description 5
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 208000006454 hepatitis Diseases 0.000 description 5
- 125000003835 nucleoside group Chemical group 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical group FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 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
- PUVKTUGKESTBDE-SECBINFHSA-N (5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-one Chemical compound CC(C)(C)[Si](C)(C)OC[C@H]1CCC(=O)O1 PUVKTUGKESTBDE-SECBINFHSA-N 0.000 description 3
- UUGITDASWNOAGG-UHFFFAOYSA-N 3-hydroxy-2-(hydroxymethyl)-2,3,3a,9a-tetrahydrofuro[1,2][1,3]oxazolo[3,4-a]pyrimidin-6-one Chemical compound O=C1C=CN2C3OC(CO)C(O)C3OC2=N1 UUGITDASWNOAGG-UHFFFAOYSA-N 0.000 description 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 3
- GYRNGMMPOKLNJO-UHFFFAOYSA-N 6-(2h-triazol-4-yl)-1h-pyrimidin-2-one Chemical class C1=CNC(=O)N=C1C1=CNN=N1 GYRNGMMPOKLNJO-UHFFFAOYSA-N 0.000 description 3
- SRBFZHDQGSBBOR-SOOFDHNKSA-N D-ribopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@@H]1O SRBFZHDQGSBBOR-SOOFDHNKSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 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 3
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 3
- 206010038997 Retroviral infections Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 108020005202 Viral DNA Proteins 0.000 description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 3
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 125000003147 glycosyl group Chemical group 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- XSSYCIGJYCVRRK-RQJHMYQMSA-N (-)-carbovir Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1C[C@H](CO)C=C1 XSSYCIGJYCVRRK-RQJHMYQMSA-N 0.000 description 2
- NSISJFFVIMQBRN-SCSAIBSYSA-N (5r)-5-(hydroxymethyl)oxolan-2-one Chemical compound OC[C@H]1CCC(=O)O1 NSISJFFVIMQBRN-SCSAIBSYSA-N 0.000 description 2
- CCZMQYGSXWZFKI-UHFFFAOYSA-N 1-chloro-4-dichlorophosphoryloxybenzene Chemical compound ClC1=CC=C(OP(Cl)(Cl)=O)C=C1 CCZMQYGSXWZFKI-UHFFFAOYSA-N 0.000 description 2
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 229930182847 D-glutamic acid Natural products 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 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 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- HMFHBZSHGGEWLO-OWMBCFKOSA-N L-ribofuranose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H]1O HMFHBZSHGGEWLO-OWMBCFKOSA-N 0.000 description 2
- 208000008771 Lymphadenopathy Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000005889 cellular cytotoxicity Effects 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 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 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- LVTHXRLARFLXNR-UHFFFAOYSA-M potassium;1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate Chemical compound [K+].[O-]S(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F LVTHXRLARFLXNR-UHFFFAOYSA-M 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- JXQQARKTHNVXBR-LJQANCHMSA-N (4r)-4-acetylsulfanyl-5-[tert-butyl(diphenyl)silyl]oxypentanoic acid Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC[C@@H](CCC(O)=O)SC(=O)C)C1=CC=CC=C1 JXQQARKTHNVXBR-LJQANCHMSA-N 0.000 description 1
- SELKWYAKRGVPAC-QGZVFWFLSA-N (4r)-5-[tert-butyl(diphenyl)silyl]oxy-4-hydroxypentanoic acid Chemical compound C=1C=CC=CC=1[Si](OC[C@H](O)CCC(O)=O)(C(C)(C)C)C1=CC=CC=C1 SELKWYAKRGVPAC-QGZVFWFLSA-N 0.000 description 1
- WLKQGVYMESXRGB-KRWDZBQOSA-N (4s)-5-[tert-butyl(diphenyl)silyl]oxy-4-iodopentanoic acid Chemical compound C=1C=CC=CC=1[Si](OC[C@@H](I)CCC(O)=O)(C(C)(C)C)C1=CC=CC=C1 WLKQGVYMESXRGB-KRWDZBQOSA-N 0.000 description 1
- BGPJLYIFDLICMR-UHFFFAOYSA-N 1,4,2,3-dioxadithiolan-5-one Chemical class O=C1OSSO1 BGPJLYIFDLICMR-UHFFFAOYSA-N 0.000 description 1
- ZSNNBSPEFVIUDS-SHYZEUOFSA-N 1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](N=[N+]=[N-])[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 ZSNNBSPEFVIUDS-SHYZEUOFSA-N 0.000 description 1
- MXHRCPNRJAMMIM-CHKWXVPMSA-N 1-[(2s,4r,5s)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-CHKWXVPMSA-N 0.000 description 1
- 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 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
- YPFDNCJJFMAZPJ-UHFFFAOYSA-N 2,6-dibromo-7h-purine Chemical compound BrC1=NC(Br)=C2NC=NC2=N1 YPFDNCJJFMAZPJ-UHFFFAOYSA-N 0.000 description 1
- BVUKXBYWLUHHHU-UHFFFAOYSA-N 2,8-dibromo-7h-purine Chemical compound BrC1=NC=C2NC(Br)=NC2=N1 BVUKXBYWLUHHHU-UHFFFAOYSA-N 0.000 description 1
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- HETOJIJPBJGZFJ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](N=[N+]=[N-])[C@@H](CO)O1 HETOJIJPBJGZFJ-KVQBGUIXSA-N 0.000 description 1
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 description 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
- 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 1
- OOBICGOWICFMIX-POYBYMJQSA-N 4-amino-1-[(2r,5s)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1C=C[C@@H](CO)O1 OOBICGOWICFMIX-POYBYMJQSA-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
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 description 1
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 1
- QFVKLKDEXOWFSL-UHFFFAOYSA-N 6-amino-5-bromo-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1Br QFVKLKDEXOWFSL-UHFFFAOYSA-N 0.000 description 1
- PNWOYKVCNDZOLS-UHFFFAOYSA-N 6-amino-5-chloro-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1Cl PNWOYKVCNDZOLS-UHFFFAOYSA-N 0.000 description 1
- UFVWJVAMULFOMC-UHFFFAOYSA-N 6-amino-5-iodo-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1I UFVWJVAMULFOMC-UHFFFAOYSA-N 0.000 description 1
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 description 1
- UGQMRVRMYYASKQ-DEGSGYPDSA-N 9-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-DEGSGYPDSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108091023043 Alu Element Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- 150000000845 D-ribose derivatives Chemical class 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 150000001100 L-ribose derivatives Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 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 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- CTDUJDNZPPZTAV-RRKCRQDMSA-N [(2r,3s,5r)-5-(6-aminopurin-9-yl)-3-fluorooxolan-2-yl]methanol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](F)[C@@H](CO)O1 CTDUJDNZPPZTAV-RRKCRQDMSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000037628 acute hepatitis B virus infection Diseases 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002529 anti-mitochondrial effect Effects 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- OIRDTQYFTABQOQ-UHFFFAOYSA-N ara-adenosine Natural products Nc1ncnc2n(cnc12)C1OC(CO)C(O)C1O OIRDTQYFTABQOQ-UHFFFAOYSA-N 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000016350 chronic hepatitis B virus infection Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- UGUZZPBNTADPIT-UHFFFAOYSA-L ethylaluminum(2+);difluoride Chemical compound [F-].[F-].CC[Al+2] UGUZZPBNTADPIT-UHFFFAOYSA-L 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 125000003843 furanosyl group Chemical group 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000012961 medicinal therapy Methods 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
- 230000004060 metabolic process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- FFFLZWJKFLYZPS-UHFFFAOYSA-N n,n-diphenylpyridin-4-amine Chemical compound C1=CC=CC=C1N(C=1C=CN=CC=1)C1=CC=CC=C1 FFFLZWJKFLYZPS-UHFFFAOYSA-N 0.000 description 1
- OGTOITXPCGGWSB-UHFFFAOYSA-N n-(2-benzamido-7h-purin-6-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(N=C1N=CNC1=1)=NC=1NC(=O)C1=CC=CC=C1 OGTOITXPCGGWSB-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- KOSYAAIZOGNATQ-UHFFFAOYSA-N o-phenyl chloromethanethioate Chemical compound ClC(=S)OC1=CC=CC=C1 KOSYAAIZOGNATQ-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000002718 pyrimidine nucleoside Substances 0.000 description 1
- 238000011158 quantitative evaluation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- 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 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000010206 sensitivity analysis Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960003636 vidarabine Drugs 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229960000523 zalcitabine Drugs 0.000 description 1
Classifications
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
-
- 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
-
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6729993A | 1993-05-25 | 1993-05-25 | |
| US8/067299 | 1993-05-25 | ||
| US08/098,650 US5627160A (en) | 1993-05-25 | 1993-07-28 | L-2',3'-dideoxy nucleoside analogs as anti-hepatitis B (HBV) and anti-HIV agents |
| US8/098650 | 1993-07-28 | ||
| PCT/US1994/005790 WO1994027616A1 (en) | 1993-05-25 | 1994-05-23 | L-2',3'-dideoxy nucleoside analogs as anti-hepatitis b (hbv) and anti-hiv agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR100279953B1 true KR100279953B1 (ko) | 2001-02-01 |
Family
ID=26747712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019950705353A Expired - Lifetime KR100279953B1 (ko) | 1993-05-25 | 1994-05-23 | 항-b형 간염 바이러스제 및 항-사람 면역결핍 바이러스제로서의 l-2',3'-디데옥시 누클레오시드 유사체 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5627160A (enExample) |
| EP (1) | EP0707481B1 (enExample) |
| JP (2) | JPH08510747A (enExample) |
| KR (1) | KR100279953B1 (enExample) |
| CN (1) | CN1076021C (enExample) |
| AT (1) | ATE195423T1 (enExample) |
| CA (1) | CA2163520C (enExample) |
| DE (1) | DE69425574T2 (enExample) |
| DK (1) | DK0707481T3 (enExample) |
| ES (1) | ES2150993T3 (enExample) |
| GR (1) | GR3034379T3 (enExample) |
| PT (1) | PT707481E (enExample) |
| WO (1) | WO1994027616A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190042484A (ko) | 2018-12-10 | 2019-04-24 | 류형준 | 바이러스 질환 개선을 위한 식품조성물 |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5827727A (en) | 1990-02-01 | 1998-10-27 | Emory University | Method of resolution of 1,3-oxathiolane nucleoside enantiomers |
| US5276151A (en) * | 1990-02-01 | 1994-01-04 | Emory University | Method of synthesis of 1,3-dioxolane nucleosides |
| US5444063A (en) * | 1990-12-05 | 1995-08-22 | Emory University | Enantiomerically pure β-D-dioxolane nucleosides with selective anti-Hepatitis B virus activity |
| US5817667A (en) * | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
| CA2637774C (en) * | 1993-09-10 | 2011-07-19 | Emory University | Nucleosides with anti-hepatitis b virus activity |
| US20020120130A1 (en) * | 1993-09-10 | 2002-08-29 | Gilles Gosselin | 2' or 3' -deoxy and 2', 3' -dideoxy-beta-L-pentofuranonucleo-side compounds, method of preparation and application in therapy, especially as anti- viral agents |
| US5587362A (en) * | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| US5512431A (en) * | 1994-06-29 | 1996-04-30 | Darwin Molecular Corporation | Methods of screening for nucleoside analogs that are incorporated by HIV reverse transcriptase and cause incorrect base pairing |
| IL115156A (en) | 1994-09-06 | 2000-07-16 | Univ Georgia | Pharmaceutical compositions for the treatment of cancer comprising 1-(2-hydroxymethyl-1,3-dioxolan-4-yl) cytosines |
| US5559101A (en) * | 1994-10-24 | 1996-09-24 | Genencor International, Inc. | L-ribofuranosyl nucleosides |
| US6391859B1 (en) | 1995-01-27 | 2002-05-21 | Emory University | [5-Carboxamido or 5-fluoro]-[2′,3′-unsaturated or 3′-modified]-pyrimidine 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 |
| US5808040A (en) * | 1995-01-30 | 1998-09-15 | Yale University | L-nucleosides incorporated into polymeric structure for stabilization of oligonucleotides |
| WO1996028162A1 (en) * | 1995-03-14 | 1996-09-19 | University Of Medicine & Dentistry Of New Jersey | New drug combination for the treatment of viral diseases |
| US5869461A (en) * | 1995-03-16 | 1999-02-09 | Yale University | Reducing toxicity of L-nucleosides with D-nucleosides |
| ATE346651T1 (de) * | 1995-06-07 | 2006-12-15 | Univ Emory | Nucleoside mit anti-hepatitis b virus wirksamkeit |
| US5753789A (en) * | 1996-07-26 | 1998-05-19 | Yale University | Oligonucleotides containing L-nucleosides |
| DE69729887T2 (de) * | 1996-10-16 | 2005-07-28 | ICN Pharmaceuticals, Inc., Costa Mesa | Purin-L-Nukleoside, Analoga und deren Verwendung |
| AU738170B2 (en) | 1996-10-16 | 2001-09-13 | Icn Pharmaceuticals, Inc. | Monocyclic L-nucleosides, analogs and uses thereof |
| US6509320B1 (en) * | 1996-10-16 | 2003-01-21 | Icn Pharmaceuticals, Inc. | Purine L-nucleosides, analogs and uses thereof |
| EP1254911A1 (en) * | 1996-10-16 | 2002-11-06 | ICN Pharmaceuticals, Inc. | Monocyclic L-nucleosides, analogs and uses thereof |
| US6090602A (en) | 1998-02-18 | 2000-07-18 | Promelas Research Corporation | Levo-monosaccharide in a nucleoside analog for use as an anti-retroviral agent |
| CN100387237C (zh) * | 1998-08-10 | 2008-05-14 | 艾丹尼克斯(开曼)有限公司 | 用于治疗乙型肝炎的β-L-2'-脱氧-核苷 |
| US7635690B2 (en) | 1999-01-22 | 2009-12-22 | Emory University | HIV-1 mutations selected for by β-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine |
| US7115584B2 (en) * | 1999-01-22 | 2006-10-03 | Emory University | HIV-1 mutations selected for by β-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine |
| US6525191B1 (en) * | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| US6436948B1 (en) | 2000-03-03 | 2002-08-20 | University Of Georgia Research Foundation Inc. | Method for the treatment of psoriasis and genital warts |
| AU2002255707A1 (en) | 2001-03-15 | 2002-10-03 | Trustees Of Boston College, The | Selective anti-viral nucleoside chain terminators |
| KR20050005442A (ko) * | 2002-04-12 | 2005-01-13 | 아칠리온 파르마세우티칼스 인코포레이티드 | β-L-플루오로-2',3'-디데히드로사이티딘(β-L-FD4C)의합성 방법 |
| US20040067877A1 (en) * | 2002-08-01 | 2004-04-08 | Schinazi Raymond F. | 2', 3'-Dideoxynucleoside analogues for the treatment or prevention of Flaviviridae infections |
| WO2005026186A1 (de) * | 2003-09-12 | 2005-03-24 | Max-Delbrück-Centrum für Molekulare Medizin | Β-l-nucleoside und ihre verwendung als pharmazeutische mittel zur behandlung viraler erkrankungen |
| EP1802315A2 (en) | 2004-10-19 | 2007-07-04 | Achillion Pharmaceuticals, Inc. | Combination therapy for treating viral infections |
| GB0513835D0 (en) * | 2005-07-07 | 2005-08-10 | Medivir Ab | HIV inhibitors |
| AU2008265397C1 (en) | 2007-06-18 | 2013-08-29 | Sunshine Lake Pharma Co., Ltd. | Bromo-phenyl substituted thiazolyl dihydropyrimidines |
| US8816074B2 (en) * | 2009-11-16 | 2014-08-26 | University of Georgia Foundation, Inc. | 2′-fluoro-6′-methylene carbocyclic nucleosides and methods of treating viral infections |
| WO2011075052A1 (en) * | 2009-12-17 | 2011-06-23 | Novadex Pharmaceuticals Ab | Novel 3´-deoxy-3´-methylidene- -l-nucleosides |
| CN102234280B (zh) * | 2010-04-26 | 2014-01-08 | 北京大学 | D,l-鸟嘌呤核苷类似物及其制备方法和应用 |
| WO2018092728A1 (ja) | 2016-11-16 | 2018-05-24 | 国立研究開発法人国立国際医療研究センター | 抗ウイルス活性等の生理活性を有するヌクレオシド誘導体 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3817982A (en) * | 1971-12-29 | 1974-06-18 | Syntex Inc | 2{40 ,3{40 -unsaturated nucleosides and method of making |
| WO1988000050A1 (en) * | 1986-07-04 | 1988-01-14 | Astra Läkemedel Aktiebolag | Novel medicinal use of nucleosides |
| US4788181A (en) * | 1986-09-29 | 1988-11-29 | The United States Of America As Represented By The Department Of Health And Human Services | 5-substituted-2',3'-dideoxycytidine compounds with anti-HTLV-III activity |
| US4861759A (en) * | 1985-08-26 | 1989-08-29 | The United States Of America As Represented By The Department Of Health And Human Services | Antiviral compositions and methods |
| US5128458A (en) * | 1990-04-20 | 1992-07-07 | Southern Research Institute | 2',3'-dideoxy-4'-thioribonucleosides as antiviral agents |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ216172A (en) * | 1985-05-15 | 1989-08-29 | Wellcome Found | Nucleosides and pharmaceutical compositions |
| US4879277A (en) * | 1985-08-26 | 1989-11-07 | The United States Of America As Represented By The Department Of Health And Human Services | Antiviral compositions and methods |
| EP0285884A3 (en) * | 1987-03-20 | 1990-07-04 | Bristol-Myers Squibb Company | process to produce 2', 3'-dideoxynucleosides |
| JPH01100191A (ja) * | 1987-10-13 | 1989-04-18 | Sanyo Kokusaku Pulp Co Ltd | 2′,3′−ジデオキシシチジン類の製造方法 |
| SE8704298D0 (sv) * | 1987-11-03 | 1987-11-03 | Astra Ab | Compounds for use in therapy |
| US4997926A (en) * | 1987-11-18 | 1991-03-05 | Scripps Clinic And Research Foundation | Deaminase-stable anti-retroviral 2-halo-2',3'-dideoxy |
| JPH07103149B2 (ja) * | 1987-11-30 | 1995-11-08 | ヤマサ醤油株式会社 | シトシン誘導体の製造法 |
| JPH02152976A (ja) * | 1988-05-06 | 1990-06-12 | Bristol Myers Co | 2´,3´―ジデヒドロ―2´,3´―ジデオキシヌクレオシドのプロドラッグ |
| SE8802687D0 (sv) * | 1988-07-20 | 1988-07-20 | Astra Ab | Nucleoside derivatives |
| JPH0269476A (ja) * | 1988-09-06 | 1990-03-08 | Kohjin Co Ltd | ピリミジン誘導体の製法 |
| 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 |
| US5444063A (en) * | 1990-12-05 | 1995-08-22 | Emory University | Enantiomerically pure β-D-dioxolane nucleosides with selective anti-Hepatitis B virus activity |
| IL100965A (en) * | 1991-02-22 | 1999-12-31 | Univ Emory | 2-Hydroxymethyl-5-(5-fluorocytosin-l-yl)-1,3-oxathiolane its resolution and pharmaceutical compositions containing it |
| ZA923641B (en) * | 1991-05-21 | 1993-02-24 | Iaf Biochem Int | Processes for the diastereoselective synthesis of nucleosides |
| AU4234193A (en) * | 1992-05-13 | 1993-12-13 | Ribozyme Pharmaceuticals, Inc. | Synthesis of nucleotide monomers |
| DE4224737A1 (de) * | 1992-07-27 | 1994-02-03 | Herbert Prof Dr Schott | Neue Cytosinnucleosidanaloga, Verfahren zu ihrer Herstellung und ihre Verwendung |
| TW356472B (en) * | 1992-09-01 | 1999-04-21 | Lilly Co Eli | A process for anomerizing nucleosides |
| GB9226927D0 (en) * | 1992-12-24 | 1993-02-17 | Iaf Biochem Int | Dideoxy nucleoside analogues |
-
1993
- 1993-07-28 US US08/098,650 patent/US5627160A/en not_active Expired - Lifetime
-
1994
- 1994-05-23 CA CA002163520A patent/CA2163520C/en not_active Expired - Fee Related
- 1994-05-23 DK DK94919207T patent/DK0707481T3/da active
- 1994-05-23 EP EP94919207A patent/EP0707481B1/en not_active Expired - Lifetime
- 1994-05-23 DE DE69425574T patent/DE69425574T2/de not_active Expired - Lifetime
- 1994-05-23 ES ES94919207T patent/ES2150993T3/es not_active Expired - Lifetime
- 1994-05-23 PT PT94919207T patent/PT707481E/pt unknown
- 1994-05-23 KR KR1019950705353A patent/KR100279953B1/ko not_active Expired - Lifetime
- 1994-05-23 JP JP7500872A patent/JPH08510747A/ja active Pending
- 1994-05-23 WO PCT/US1994/005790 patent/WO1994027616A1/en not_active Ceased
- 1994-05-23 AT AT94919207T patent/ATE195423T1/de not_active IP Right Cessation
- 1994-05-24 CN CN94106188A patent/CN1076021C/zh not_active Expired - Lifetime
-
2000
- 2000-09-08 GR GR20000402067T patent/GR3034379T3/el unknown
-
2004
- 2004-03-31 JP JP2004106919A patent/JP2004244422A/ja active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3817982A (en) * | 1971-12-29 | 1974-06-18 | Syntex Inc | 2{40 ,3{40 -unsaturated nucleosides and method of making |
| US4861759A (en) * | 1985-08-26 | 1989-08-29 | The United States Of America As Represented By The Department Of Health And Human Services | Antiviral compositions and methods |
| WO1988000050A1 (en) * | 1986-07-04 | 1988-01-14 | Astra Läkemedel Aktiebolag | Novel medicinal use of nucleosides |
| US4788181A (en) * | 1986-09-29 | 1988-11-29 | The United States Of America As Represented By The Department Of Health And Human Services | 5-substituted-2',3'-dideoxycytidine compounds with anti-HTLV-III activity |
| US5128458A (en) * | 1990-04-20 | 1992-07-07 | Southern Research Institute | 2',3'-dideoxy-4'-thioribonucleosides as antiviral agents |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190042484A (ko) | 2018-12-10 | 2019-04-24 | 류형준 | 바이러스 질환 개선을 위한 식품조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU693795B2 (en) | 1998-07-09 |
| CN1076021C (zh) | 2001-12-12 |
| WO1994027616A1 (en) | 1994-12-08 |
| DK0707481T3 (da) | 2000-10-30 |
| ES2150993T3 (es) | 2000-12-16 |
| AU7043094A (en) | 1994-12-20 |
| GR3034379T3 (en) | 2000-12-29 |
| DE69425574T2 (de) | 2001-01-04 |
| EP0707481A4 (enExample) | 1996-05-29 |
| EP0707481A1 (en) | 1996-04-24 |
| EP0707481B1 (en) | 2000-08-16 |
| CA2163520A1 (en) | 1994-12-08 |
| CN1100303A (zh) | 1995-03-22 |
| CA2163520C (en) | 2006-01-10 |
| JPH08510747A (ja) | 1996-11-12 |
| DE69425574D1 (en) | 2000-09-21 |
| PT707481E (pt) | 2001-02-28 |
| ATE195423T1 (de) | 2000-09-15 |
| US5627160A (en) | 1997-05-06 |
| HK1013257A1 (en) | 1999-10-22 |
| JP2004244422A (ja) | 2004-09-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5627160A (en) | L-2',3'-dideoxy nucleoside analogs as anti-hepatitis B (HBV) and anti-HIV agents | |
| US5561120A (en) | Method for treating HBV infections with L-2',3'-didehydro-dideoxy-5-fluorocytidine | |
| EP2298783B1 (en) | Anti-viral nucleoside analogs and methods for treating viral infections, especially hiv infections | |
| US6153594A (en) | 5'-O-acylated antiviral nucleosides | |
| EP0322384B1 (en) | Nucleosides for use in therapy | |
| US6833361B2 (en) | Nucleosides having bicyclic sugar moiety | |
| US5559101A (en) | L-ribofuranosyl nucleosides | |
| Lee et al. | Structure− activity relationships of 2 ‘-fluoro-2 ‘, 3 ‘-unsaturated D-nucleosides as anti-HIV-1 agents | |
| JPH03504969A (ja) | ピリミジン誘導体 | |
| WO1994009793A1 (en) | ENANTIOMERICALLY PURE β-D-DIOXOLANE NUCLEOSIDES WITH SELECTIVE ANTI-HEPATITIS B VIRUS ACTIVITY | |
| JPH03148292A (ja) | B型肝炎に対する製薬剤として、ピリミジンヌクレオシド及びプリンヌクレオシドを製造する為の方法及びその使用法 | |
| GB2260319A (en) | Nucleoside ester antiviral agents | |
| AU693795C (en) | L-2',3'-dideoxy nucleoside analogs as anti-hepatitis B (HBV)and anti-HIV agents | |
| US6914052B2 (en) | Selective anti-viral nucleoside chain terminators | |
| EP0799834A1 (en) | Modified nucleotides | |
| HK1013257B (en) | L-2',3'-dideoxy nucleoside analogs as anti-hepatitis b (hbv) and anti-hiv agents | |
| AU672369C (en) | Chemical compounds | |
| EP0309560A1 (en) | NUCLEOSIDES AND NUCLEOSIDE ANALOGS, COMPOSITIONS AND PHARMACEUTICAL METHODS FOR PREPARING THE COMPOUNDS. | |
| HK1053841A (en) | Monocyclic l-nucleosides, analogs and uses thereof | |
| HK1003437B (en) | Antiviral compounds | |
| HK1007430B (en) | Nucleosides being o-acylated with a mono-unsaturated omega-9 c18 or c20 fatty acid | |
| HK1050901A (en) | Monocyclic l-nucleosides, analogs and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 19951125 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 19980213 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 19991129 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20000819 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20001106 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20001107 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20030313 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20040407 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20050519 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20061020 Start annual number: 7 End annual number: 7 |
|
| PR1001 | Payment of annual fee |
Payment date: 20071015 Start annual number: 8 End annual number: 8 |
|
| PR1001 | Payment of annual fee |
Payment date: 20081024 Start annual number: 9 End annual number: 9 |
|
| PR1001 | Payment of annual fee |
Payment date: 20091022 Start annual number: 10 End annual number: 10 |
|
| PR1001 | Payment of annual fee |
Payment date: 20101027 Start annual number: 11 End annual number: 11 |
|
| PR1001 | Payment of annual fee |
Payment date: 20111026 Start annual number: 12 End annual number: 12 |
|
| FPAY | Annual fee payment |
Payment date: 20121023 Year of fee payment: 13 |
|
| PR1001 | Payment of annual fee |
Payment date: 20121023 Start annual number: 13 End annual number: 13 |
|
| FPAY | Annual fee payment |
Payment date: 20131023 Year of fee payment: 14 |
|
| PR1001 | Payment of annual fee |
Payment date: 20131023 Start annual number: 14 End annual number: 14 |
|
| EXPY | Expiration of term | ||
| PC1801 | Expiration of term |
Termination date: 20141123 Termination category: Expiration of duration |