IL84477A - History of Phosphonomethoxyalkylene Purinopyrimidine and Pharmaceutical Preparations Containing Them - Google Patents
History of Phosphonomethoxyalkylene Purinopyrimidine and Pharmaceutical Preparations Containing ThemInfo
- Publication number
- IL84477A IL84477A IL8447787A IL8447787A IL84477A IL 84477 A IL84477 A IL 84477A IL 8447787 A IL8447787 A IL 8447787A IL 8447787 A IL8447787 A IL 8447787A IL 84477 A IL84477 A IL 84477A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- hydrogen
- guanine
- alk
- compounds
- Prior art date
Links
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 3
- 150000003230 pyrimidines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 102
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
- -1 8-cWoroguanine Chemical compound 0.000 claims description 28
- 230000000840 anti-viral effect Effects 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 16
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 10
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical group C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 claims description 8
- 229940113082 thymine Drugs 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 150000001450 anions Chemical class 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 4
- 229940035893 uracil Drugs 0.000 claims description 4
- CRYCZDRIXVHNQB-UHFFFAOYSA-N 2-amino-8-bromo-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(Br)N2 CRYCZDRIXVHNQB-UHFFFAOYSA-N 0.000 claims description 3
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims description 3
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- BLXGZIDBSXVMLU-OWOJBTEDSA-N 5-[(e)-2-bromoethenyl]-1h-pyrimidine-2,4-dione Chemical group Br\C=C\C1=CNC(=O)NC1=O BLXGZIDBSXVMLU-OWOJBTEDSA-N 0.000 claims description 2
- 229910052987 metal hydride Inorganic materials 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 229940075420 xanthine Drugs 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 7
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- WYDKPTZGVLTYPG-UHFFFAOYSA-N 2,8-diamino-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(N)N2 WYDKPTZGVLTYPG-UHFFFAOYSA-N 0.000 claims 1
- YCFWZXAEOXKNHL-UHFFFAOYSA-N 2-amino-8-chloro-3,7-dihydropurin-6-one Chemical group N1C(N)=NC(=O)C2=C1N=C(Cl)N2 YCFWZXAEOXKNHL-UHFFFAOYSA-N 0.000 claims 1
- TXGWTBFCLADKKR-UHFFFAOYSA-N 2-amino-8-hydrazinyl-3,7-dihydropurin-6-one Chemical compound N1=C(N)NC(=O)C2=C1N=C(NN)N2 TXGWTBFCLADKKR-UHFFFAOYSA-N 0.000 claims 1
- DJGMEMUXTWZGIC-UHFFFAOYSA-N 2-amino-8-methyl-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(C)N2 DJGMEMUXTWZGIC-UHFFFAOYSA-N 0.000 claims 1
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 claims 1
- BLXGZIDBSXVMLU-UHFFFAOYSA-N 5-(2-bromoethenyl)-1h-pyrimidine-2,4-dione Chemical compound BrC=CC1=CNC(=O)NC1=O BLXGZIDBSXVMLU-UHFFFAOYSA-N 0.000 claims 1
- ZRYZBEQILKESAW-UHFFFAOYSA-N 5-ethenyl-1h-pyrimidine-2,4-dione Chemical compound C=CC1=CNC(=O)NC1=O ZRYZBEQILKESAW-UHFFFAOYSA-N 0.000 claims 1
- RHIULBJJKFDJPR-UHFFFAOYSA-N 5-ethyl-1h-pyrimidine-2,4-dione Chemical compound CCC1=CNC(=O)NC1=O RHIULBJJKFDJPR-UHFFFAOYSA-N 0.000 claims 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 1
- CZJGCEGNCSGRBI-UHFFFAOYSA-N 6-amino-5-ethyl-1h-pyrimidin-2-one Chemical compound CCC1=CNC(=O)N=C1N CZJGCEGNCSGRBI-UHFFFAOYSA-N 0.000 claims 1
- CLGFIVUFZRGQRP-UHFFFAOYSA-N 7,8-dihydro-8-oxoguanine Chemical compound O=C1NC(N)=NC2=C1NC(=O)N2 CLGFIVUFZRGQRP-UHFFFAOYSA-N 0.000 claims 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims 1
- 229960003087 tioguanine Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- 239000000243 solution Substances 0.000 description 45
- 239000000203 mixture Substances 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 239000000543 intermediate Substances 0.000 description 24
- 239000000047 product Substances 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000002002 slurry Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- SPSDEXPWUORORO-UHFFFAOYSA-N 2-amino-9-[2-(diethoxyphosphorylmethoxy)ethyl]-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N(CCOCP(=O)(OCC)OCC)C=N2 SPSDEXPWUORORO-UHFFFAOYSA-N 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000005690 diesters Chemical class 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 5
- 241000700584 Simplexvirus Species 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 4
- 241000714177 Murine leukemia virus Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229960000643 adenine Drugs 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- VPFMQXUAXRIYDG-UHFFFAOYSA-N 1-bromo-4-(diethoxyphosphorylmethoxy)butane Chemical compound CCOP(=O)(OCC)COCCCCBr VPFMQXUAXRIYDG-UHFFFAOYSA-N 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- MSCDPPZMQRATKR-UHFFFAOYSA-N 2-(propylamino)-3,7-dihydropurin-6-one Chemical compound N1C(NCCC)=NC(=O)C2=C1N=CN2 MSCDPPZMQRATKR-UHFFFAOYSA-N 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 238000002962 plaque-reduction assay Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- ATJHEGFVOKHRPN-UHFFFAOYSA-N 2-(diethoxyphosphorylmethoxy)ethanol Chemical compound CCOP(=O)(OCC)COCCO ATJHEGFVOKHRPN-UHFFFAOYSA-N 0.000 description 2
- UJRVYFSGHYCOKQ-UHFFFAOYSA-N 2-(diethoxyphosphorylmethoxy)ethyl methanesulfonate Chemical compound CCOP(=O)(OCC)COCCOS(C)(=O)=O UJRVYFSGHYCOKQ-UHFFFAOYSA-N 0.000 description 2
- OZJYUMCRPONPPS-UHFFFAOYSA-N 2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-phenylmethoxypropan-1-ol Chemical compound CC(C)(C)[Si](C)(C)OCC(CO)COCC1=CC=CC=C1 OZJYUMCRPONPPS-UHFFFAOYSA-N 0.000 description 2
- FGSXDBQWHXPDSQ-UHFFFAOYSA-N 4-(6-aminopurin-9-yl)butoxymethylphosphonic acid Chemical compound NC1=NC=NC2=C1N=CN2CCCCOCP(O)(O)=O FGSXDBQWHXPDSQ-UHFFFAOYSA-N 0.000 description 2
- KZWLVSQKGSLLNU-UHFFFAOYSA-N 5-hydroxypentyl methanesulfonate Chemical compound CS(=O)(=O)OCCCCCO KZWLVSQKGSLLNU-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- XJEAKZREOVQGTD-UHFFFAOYSA-N [2-(diethoxyphosphorylmethoxymethyl)-3-phenylmethoxypropyl] 4-methylbenzenesulfonate Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)OCC(COCP(=O)(OCC)OCC)COCC1=CC=CC=C1 XJEAKZREOVQGTD-UHFFFAOYSA-N 0.000 description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229940121357 antivirals Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 2
- BNKDGTGYTVFGBY-UHFFFAOYSA-N diethoxyphosphorylmethyl trifluoromethanesulfonate Chemical compound CCOP(=O)(OCC)COS(=O)(=O)C(F)(F)F BNKDGTGYTVFGBY-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- DRSMAJIXTNZPIC-UHFFFAOYSA-N tert-butyl-[2-(diethoxyphosphorylmethoxymethyl)-3-phenylmethoxypropoxy]-dimethylsilane Chemical compound CCOP(=O)(OCC)COCC(CO[Si](C)(C)C(C)(C)C)COCC1=CC=CC=C1 DRSMAJIXTNZPIC-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 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
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 210000003501 vero cell Anatomy 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- XMVOEDCIKAXDHL-UHFFFAOYSA-M (2-amino-7h-purin-6-yl)-trimethylazanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=NC(N)=NC2=C1N=CN2 XMVOEDCIKAXDHL-UHFFFAOYSA-M 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- 229940043375 1,5-pentanediol Drugs 0.000 description 1
- KZVJZSUMHWFPIC-UHFFFAOYSA-N 1-(diethoxyphosphorylmethoxy)-2-iodoethane Chemical compound CCOP(=O)(OCC)COCCI KZVJZSUMHWFPIC-UHFFFAOYSA-N 0.000 description 1
- HJAYIRIYASVMFY-UHFFFAOYSA-N 1-bromo-4-(chloromethoxy)butane Chemical compound ClCOCCCCBr HJAYIRIYASVMFY-UHFFFAOYSA-N 0.000 description 1
- PERFIQYTXCWMBE-UHFFFAOYSA-N 2-(2-amino-6-oxo-3h-purin-9-yl)ethoxymethyl-ethoxyphosphinic acid Chemical compound N1C(N)=NC(=O)C2=C1N(CCOCP(O)(=O)OCC)C=N2 PERFIQYTXCWMBE-UHFFFAOYSA-N 0.000 description 1
- CKRRYAIPNKLRQU-UHFFFAOYSA-N 2-(diethoxyphosphorylmethoxymethyl)-3-phenylmethoxypropan-1-ol Chemical compound CCOP(=O)(OCC)COCC(CO)COCC1=CC=CC=C1 CKRRYAIPNKLRQU-UHFFFAOYSA-N 0.000 description 1
- LFCHIGIKBKLZIS-UHFFFAOYSA-N 2-(ethylamino)-3,7-dihydropurin-6-one Chemical compound N1C(NCC)=NC(=O)C2=C1N=CN2 LFCHIGIKBKLZIS-UHFFFAOYSA-N 0.000 description 1
- UMRWMXZIGBWCQD-UHFFFAOYSA-N 2-(phenylmethoxymethyl)propane-1,3-diol Chemical compound OCC(CO)COCC1=CC=CC=C1 UMRWMXZIGBWCQD-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- USCCECGPGBGFOM-UHFFFAOYSA-N 2-propyl-7h-purin-6-amine Chemical compound CCCC1=NC(N)=C2NC=NC2=N1 USCCECGPGBGFOM-UHFFFAOYSA-N 0.000 description 1
- PDGJLVDPRKRLFL-UHFFFAOYSA-N 3,3,4,4-tetramethyl-2-(phenylmethoxymethyl)-1-silyloxypentan-1-ol Chemical compound C(C1=CC=CC=C1)OCC(C(O)O[SiH3])C(C(C)(C)C)(C)C PDGJLVDPRKRLFL-UHFFFAOYSA-N 0.000 description 1
- BEZZJJXROBUBSH-UHFFFAOYSA-N 5-(diethoxyphosphorylmethoxy)pentyl methanesulfonate Chemical compound CCOP(=O)(OCC)COCCCCCOS(C)(=O)=O BEZZJJXROBUBSH-UHFFFAOYSA-N 0.000 description 1
- NALREUIWICQLPS-UHFFFAOYSA-N 7-imino-n,n-dimethylphenothiazin-3-amine;hydrochloride Chemical compound [Cl-].C1=C(N)C=C2SC3=CC(=[N+](C)C)C=CC3=NC2=C1 NALREUIWICQLPS-UHFFFAOYSA-N 0.000 description 1
- 101150052147 ALLC gene Proteins 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VJTRNPJZCYUVQY-UHFFFAOYSA-N C(C1=CC=CC=C1)OCC(C(O)OC)CP(=O)(OCC)OCC Chemical compound C(C1=CC=CC=C1)OCC(C(O)OC)CP(=O)(OCC)OCC VJTRNPJZCYUVQY-UHFFFAOYSA-N 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical group CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011416 Croup infectious Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group 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 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- ALQSHHUCVQOPAS-UHFFFAOYSA-N Pentane-1,5-diol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 102000005686 Serum Globulins Human genes 0.000 description 1
- 108010045362 Serum Globulins Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003602 anti-herpes Effects 0.000 description 1
- 238000002832 anti-viral assay Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004651 chloromethoxy group Chemical group ClCO* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 201000010549 croup Diseases 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- UOEFFQWLRUBDME-UHFFFAOYSA-N diethoxyphosphorylmethyl 4-methylbenzenesulfonate Chemical compound CCOP(=O)(OCC)COS(=O)(=O)C1=CC=C(C)C=C1 UOEFFQWLRUBDME-UHFFFAOYSA-N 0.000 description 1
- SULWMEGSVQCTSK-UHFFFAOYSA-N diethyl hydrogen phosphite Chemical compound CCOP(O)OCC SULWMEGSVQCTSK-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- MXSMRDDXWJSGMC-UHFFFAOYSA-N n-(6-oxo-3,7-dihydropurin-2-yl)acetamide Chemical compound N1C(NC(=O)C)=NC(=O)C2=C1N=CN2 MXSMRDDXWJSGMC-UHFFFAOYSA-N 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N pentofuranose Chemical compound OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 125000004413 phosphonomethoxyalkyl group Chemical group 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- KFKKMTSZBPPWTO-UHFFFAOYSA-N purine-2,5-diamine Chemical compound C1=NC(N)=NC2=NC=NC21N KFKKMTSZBPPWTO-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- LZTRCELOJRDYMQ-UHFFFAOYSA-N triphenylmethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1=CC=CC=C1 LZTRCELOJRDYMQ-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 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 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93211286A | 1986-11-18 | 1986-11-18 | |
| US11434087A | 1987-11-04 | 1987-11-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL84477A true IL84477A (en) | 1995-12-08 |
Family
ID=26812069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL8447787A IL84477A (en) | 1986-11-18 | 1987-11-16 | History of Phosphonomethoxyalkylene Purinopyrimidine and Pharmaceutical Preparations Containing Them |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0269947B2 (xx) |
| JP (1) | JP2593895B2 (xx) |
| KR (1) | KR950009195B1 (xx) |
| AU (1) | AU613592B2 (xx) |
| CA (1) | CA1339780C (xx) |
| DE (1) | DE3780581T3 (xx) |
| DK (1) | DK170049B1 (xx) |
| EG (1) | EG19346A (xx) |
| ES (1) | ES2033774T5 (xx) |
| GR (2) | GR3005256T3 (xx) |
| IL (1) | IL84477A (xx) |
| NZ (1) | NZ222553A (xx) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS264222B1 (en) * | 1986-07-18 | 1989-06-13 | Holy Antonin | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
| IL84477A (en) * | 1986-11-18 | 1995-12-08 | Bristol Myers Squibb Co | History of Phosphonomethoxyalkylene Purinopyrimidine and Pharmaceutical Preparations Containing Them |
| EP0338168A1 (en) * | 1988-04-19 | 1989-10-25 | Merrell Dow Pharmaceuticals Inc. | Phosphonoalkylpurine derivatives |
| US5266722A (en) * | 1988-11-09 | 1993-11-30 | W. R. Grace & Co.-Conn. | Polyether bis-phosphonic acid compounds |
| US5688778A (en) * | 1989-05-15 | 1997-11-18 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Nucleoside analogs |
| DE69110528T2 (de) * | 1990-04-20 | 1996-03-14 | Inst Of Organic Chemistry And | Chirale 2-(Phosphonomethoxy)propyl-Guanine als antivirale Agentien. |
| US5302585A (en) * | 1990-04-20 | 1994-04-12 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents |
| CZ285420B6 (cs) * | 1990-04-24 | 1999-08-11 | Ústav Organické Chemie A Biochemie Avčr | N-(3-Fluor-2-fosfonylmethoxypropyl)deriváty purinových a pyrimidinových heterocyklických bazí, způsoby jejich přípravy a použití |
| EP0481214B1 (en) * | 1990-09-14 | 1998-06-24 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Prodrugs of phosphonates |
| US5208221A (en) * | 1990-11-29 | 1993-05-04 | Bristol-Myers Squibb Company | Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives |
| CZ287745B6 (cs) * | 1991-10-11 | 2001-01-17 | Ústav organické chemie a biochemie AV ČR | Acyklické fosfonomethoxyalkylsubstituované alkenylové a alkinylové deriváty purinu a pyrimidinu |
| US6057305A (en) * | 1992-08-05 | 2000-05-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiretroviral enantiomeric nucleotide analogs |
| JPH09506333A (ja) * | 1993-09-17 | 1997-06-24 | ギリアード サイエンシーズ，インコーポレイテッド | 治療化合物の投薬方法 |
| US5656745A (en) * | 1993-09-17 | 1997-08-12 | Gilead Sciences, Inc. | Nucleotide analogs |
| US5798340A (en) * | 1993-09-17 | 1998-08-25 | Gilead Sciences, Inc. | Nucleotide analogs |
| IT1270008B (it) * | 1994-09-23 | 1997-04-16 | Ist Superiore Sanita | Derivati purinici ed 8-azapurinici atti al trattamento terapeutico dell'aids |
| US5977061A (en) * | 1995-04-21 | 1999-11-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | N6 - substituted nucleotide analagues and their use |
| US5717095A (en) * | 1995-12-29 | 1998-02-10 | Gilead Sciences, Inc. | Nucleotide analogs |
| CA2261619C (en) * | 1996-07-26 | 2006-05-23 | Gilead Sciences, Inc. | Nucleotide analogs |
| US5922695A (en) * | 1996-07-26 | 1999-07-13 | Gilead Sciences, Inc. | Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability |
| AU740264C (en) * | 1997-09-11 | 2002-06-06 | Commonwealth Scientific And Industrial Research Organisation | Antiviral agents |
| IL159494A0 (en) | 2001-06-29 | 2004-06-01 | Acad Of Science Czech Republic | 6-2'-(phosphonomethoxy) alkoxy pyrimidine derivatives having antiviral activity |
| WO2003087298A2 (en) * | 2001-11-14 | 2003-10-23 | Biocryst Pharmaceuticals, Inc. | Nucleosides preparation thereof and use as inhibitors of rna viral polymerases |
| US7388002B2 (en) | 2001-11-14 | 2008-06-17 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
| AU2004206827A1 (en) | 2003-01-14 | 2004-08-05 | Gilead Sciences, Inc. | Compositions and methods for combination antiviral therapy |
| US7371852B2 (en) | 2003-01-22 | 2008-05-13 | Serenex, Inc. | Alkyl-linked nucleotide compositions |
| CA2527805C (en) | 2003-06-16 | 2012-08-21 | Institute Of Organic Chemistry And Biochemistry, Academy Of Sciences Of The Czech Republic | Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs |
| US20060252729A1 (en) | 2003-07-30 | 2006-11-09 | Krawczyk Steven H | Nucleobase phosphonate analogs for antiviral treatment |
| WO2005090370A1 (en) | 2004-02-05 | 2005-09-29 | The Regents Of The University Of California | Pharmacologically active agents containing esterified phosphonates and methods for use thereof |
| TWI375560B (en) | 2005-06-13 | 2012-11-01 | Gilead Sciences Inc | Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same |
| TWI471145B (zh) | 2005-06-13 | 2015-02-01 | Bristol Myers Squibb & Gilead Sciences Llc | 單一式藥學劑量型 |
| TWI444384B (zh) | 2008-02-20 | 2014-07-11 | Gilead Sciences Inc | 核苷酸類似物及其在治療惡性腫瘤上的用途 |
| MX2013006127A (es) | 2010-12-10 | 2013-09-26 | Sigmapharm Lab Llc | Composiciones sumamente estables de analogos nucleotidicoas oralmente activos o profarmacos analogos nucleotidicos oralmente activos. |
| DK2794624T3 (da) | 2011-12-22 | 2019-07-22 | Geron Corp | Guanin-analoger som telomerase-substrater og påvirkere af telomer-længde |
| CN103665043B (zh) | 2012-08-30 | 2017-11-10 | 江苏豪森药业集团有限公司 | 一种替诺福韦前药及其在医药上的应用 |
| EP3194411B1 (en) * | 2014-09-15 | 2022-05-04 | The Regents of the University of California | Nucleotide analogs |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS233665B1 (en) * | 1983-01-06 | 1985-03-14 | Antonin Holy | Processing of isomere o-phosphonylmethylderivative of anantiomere racemic vicinal diene |
| CS263952B1 (en) * | 1985-04-25 | 1989-05-12 | Holy Antonin | Remedy with antiviral effect |
| CS263951B1 (en) * | 1985-04-25 | 1989-05-12 | Antonin Holy | 9-(phosponylmethoxyalkyl)adenines and method of their preparation |
| CS264222B1 (en) * | 1986-07-18 | 1989-06-13 | Holy Antonin | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
| IL84477A (en) * | 1986-11-18 | 1995-12-08 | Bristol Myers Squibb Co | History of Phosphonomethoxyalkylene Purinopyrimidine and Pharmaceutical Preparations Containing Them |
-
1987
- 1987-11-16 IL IL8447787A patent/IL84477A/en not_active IP Right Cessation
- 1987-11-16 AU AU81250/87A patent/AU613592B2/en not_active Expired
- 1987-11-16 NZ NZ222553A patent/NZ222553A/en unknown
- 1987-11-17 EG EG65887A patent/EG19346A/xx active
- 1987-11-17 DK DK604087A patent/DK170049B1/da not_active IP Right Cessation
- 1987-11-17 DE DE3780581T patent/DE3780581T3/de not_active Expired - Lifetime
- 1987-11-17 JP JP62290469A patent/JP2593895B2/ja not_active Expired - Lifetime
- 1987-11-17 ES ES87116996T patent/ES2033774T5/es not_active Expired - Lifetime
- 1987-11-17 CA CA000551979A patent/CA1339780C/en not_active Expired - Lifetime
- 1987-11-17 EP EP87116996A patent/EP0269947B2/en not_active Expired - Lifetime
- 1987-11-18 KR KR1019870012967A patent/KR950009195B1/ko not_active IP Right Cessation
-
1992
- 1992-07-23 GR GR920401473T patent/GR3005256T3/el unknown
-
1996
- 1996-10-17 GR GR960400474T patent/GR3021389T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63170388A (ja) | 1988-07-14 |
| KR880006256A (ko) | 1988-07-22 |
| NZ222553A (en) | 1991-07-26 |
| AU8125087A (en) | 1988-05-19 |
| JP2593895B2 (ja) | 1997-03-26 |
| DK604087A (da) | 1988-05-19 |
| KR950009195B1 (ko) | 1995-08-16 |
| AU613592B2 (en) | 1991-08-08 |
| DE3780581T2 (de) | 1992-12-17 |
| ES2033774T3 (es) | 1993-04-01 |
| DE3780581T3 (de) | 1997-06-05 |
| DE3780581D1 (de) | 1992-08-27 |
| GR3005256T3 (en) | 1993-05-24 |
| EP0269947B1 (en) | 1992-07-22 |
| EP0269947A1 (en) | 1988-06-08 |
| ES2033774T5 (es) | 1997-03-16 |
| CA1339780C (en) | 1998-03-24 |
| DK604087D0 (da) | 1987-11-17 |
| EG19346A (en) | 1995-01-31 |
| GR3021389T3 (en) | 1997-01-31 |
| DK170049B1 (da) | 1995-05-08 |
| EP0269947B2 (en) | 1996-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0269947B1 (en) | Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives | |
| US5854228A (en) | Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives | |
| CA2479846C (en) | Phosphonomethoxymethylpurine/pyrimidine derivatives | |
| US5663159A (en) | Prodrugs of phosphonates | |
| US5386030A (en) | Antiviral (phosphonomethoxy)methoxy purine/pyrimidine derivatives | |
| Kim et al. | Acyclic purine phosphonate analogs as antiviral agents. Synthesis and structure-activity relationships | |
| US5817647A (en) | Unsaturated acetylene phosphonate derivatives of purines | |
| US5837871A (en) | Nucleoside analogs | |
| Yu et al. | Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy) ethyl] guanine | |
| AU681395B2 (en) | Unsaturated phosphonates derivatives of purines and pyrimidines | |
| AU661347B2 (en) | Antiviral acyclic phosphonomethoxyalkyl substituted, alkenyl and alkynyl purine and pyrimidine derivatives | |
| JP3172801B2 (ja) | 抗ウィルス剤としてのキラル２−（ホスホノメトキシ）プロピルグアニン | |
| CA2015671C (en) | Phosphonomethoxytetrahydrofuranyl-purine/pyrimidine derivatives | |
| AU646594B2 (en) | Nucleoside analogs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HP | Change in proprietorship | ||
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXP | Patent expired |