CA1086316A - Purine acyclic nucleosides - Google Patents
Purine acyclic nucleosidesInfo
- Publication number
- CA1086316A CA1086316A CA272,888A CA272888A CA1086316A CA 1086316 A CA1086316 A CA 1086316A CA 272888 A CA272888 A CA 272888A CA 1086316 A CA1086316 A CA 1086316A
- Authority
- CA
- Canada
- Prior art keywords
- group
- formula
- process according
- compound
- amino
- 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
Links
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title claims description 12
- 239000002777 nucleoside Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 62
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 8
- 125000004429 atom Chemical group 0.000 claims abstract description 5
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000002252 acyl group Chemical group 0.000 claims description 15
- -1 alkali metal salt Chemical class 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 150000003212 purines Chemical class 0.000 claims description 10
- 230000000903 blocking effect Effects 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- JGSACAANCVVBKM-UHFFFAOYSA-N 2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]ethyl propanoate Chemical compound N1=C(N)NC(=O)C2=C1N(COCCOC(=O)CC)C=N2 JGSACAANCVVBKM-UHFFFAOYSA-N 0.000 claims description 7
- 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 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- 229910052783 alkali metal Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- TYHQCBMIGOIZEH-UHFFFAOYSA-N 2-[(2,6-diaminopurin-9-yl)methoxy]ethyl formate Chemical compound NC1=NC(N)=C2N=CN(COCCOC=O)C2=N1 TYHQCBMIGOIZEH-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- HVPBQEYFXWIYBP-UHFFFAOYSA-N 2-(chloromethoxy)ethyl propanoate Chemical compound C(CC)(=O)OCCOCCl HVPBQEYFXWIYBP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001340 alkali metals Chemical group 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 238000006894 reductive elimination reaction Methods 0.000 claims description 3
- 238000005809 transesterification reaction Methods 0.000 claims description 3
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 claims description 2
- CSMCRCLIPQDIKB-UHFFFAOYSA-N 2-[(2,6-diaminopurin-9-yl)methoxy]ethanol Chemical compound NC1=NC(N)=C2N=CN(COCCO)C2=N1 CSMCRCLIPQDIKB-UHFFFAOYSA-N 0.000 claims description 2
- 238000006136 alcoholysis reaction Methods 0.000 claims description 2
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 238000003797 solvolysis reaction Methods 0.000 claims description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- OFDJYPIEYXKRHP-UHFFFAOYSA-N 2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]ethyl formate Chemical compound O=C1NC(N)=NC2=C1N=CN2COCCOC=O OFDJYPIEYXKRHP-UHFFFAOYSA-N 0.000 claims 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims 2
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims 1
- 238000010531 catalytic reduction reaction Methods 0.000 claims 1
- 230000000840 anti-viral effect Effects 0.000 abstract description 4
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 abstract description 3
- 241000700605 Viruses Species 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 239000000203 mixture Substances 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 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 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000007916 tablet composition Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010438 heat treatment Methods 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
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- AIUZWPFLGQMINO-UHFFFAOYSA-N 2-(chloromethoxy)ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOCCl AIUZWPFLGQMINO-UHFFFAOYSA-N 0.000 description 2
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000000375 suspending agent Substances 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
- 230000003612 virological effect Effects 0.000 description 2
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
- QWXRKGCSTOAWIV-UHFFFAOYSA-N 2-(ethoxymethylamino)-3,7-dihydropurin-6-one Chemical compound N1C(NCOCC)=NC(=O)C2=C1N=CN2 QWXRKGCSTOAWIV-UHFFFAOYSA-N 0.000 description 1
- IFLLOYOADZYYGC-UHFFFAOYSA-N 2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethyl 3-chlorobenzoate Chemical compound ClC=1C=C(C(=O)OCCOCN2C=3N=C(NC(C=3N=C2)=O)N)C=CC=1 IFLLOYOADZYYGC-UHFFFAOYSA-N 0.000 description 1
- SLVUVSMVSSTFHH-UHFFFAOYSA-N 2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]ethyl hexanoate Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)CCCCC)C=N2 SLVUVSMVSSTFHH-UHFFFAOYSA-N 0.000 description 1
- IVXUOOVXNYSWEX-UHFFFAOYSA-N 2-[(2-amino-6-oxo-3h-purin-9-yl)methoxy]ethyl tridecanoate Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)CCCCCCCCCCCC)C=N2 IVXUOOVXNYSWEX-UHFFFAOYSA-N 0.000 description 1
- JPFMNESGLYNBJP-UHFFFAOYSA-N 2-amino-9-[2-(4-methylphenoxy)ethoxymethyl]-1H-purin-6-one Chemical compound C1(=CC=C(C=C1)OCCOCN1C=2N=C(NC(C=2N=C1)=O)N)C JPFMNESGLYNBJP-UHFFFAOYSA-N 0.000 description 1
- CTXGTHVAWRBISV-UHFFFAOYSA-N 2-hydroxyethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCO CTXGTHVAWRBISV-UHFFFAOYSA-N 0.000 description 1
- SFAMKDPMPDEXGH-UHFFFAOYSA-N 2-hydroxyethyl propanoate Chemical compound CCC(=O)OCCO SFAMKDPMPDEXGH-UHFFFAOYSA-N 0.000 description 1
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 208000005100 Herpetic Keratitis Diseases 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010073938 Ophthalmic herpes simplex Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- DSRXQXXHDIAVJT-UHFFFAOYSA-N acetonitrile;n,n-dimethylformamide Chemical compound CC#N.CN(C)C=O DSRXQXXHDIAVJT-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 101150057036 acyI gene Proteins 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 208000011323 eye infectious disease Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 201000010884 herpes simplex virus keratitis Diseases 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- FJRPWCNFWGBGOF-UHFFFAOYSA-N tridecanoyl chloride Chemical compound CCCCCCCCCCCCC(Cl)=O FJRPWCNFWGBGOF-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- 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
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7988/76A GB1561380A (en) | 1976-03-01 | 1976-03-01 | Esters of hydroxyalkoxyalkyl purines their preparation and pharmaceutical compositions containing them |
| GB7988/76 | 1976-03-01 | ||
| US71810576A | 1976-08-27 | 1976-08-27 | |
| US718,105 | 1976-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1086316A true CA1086316A (en) | 1980-09-23 |
Family
ID=26241801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA272,888A Expired CA1086316A (en) | 1976-03-01 | 1977-03-01 | Purine acyclic nucleosides |
Country Status (25)
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8202626A (nl) * | 1982-06-29 | 1984-01-16 | Stichting Rega V Z W | Derivaten van 9-(2-hydroxyethoxymethyl)guanine. |
| ES520140A0 (es) * | 1983-02-25 | 1984-04-01 | Ind Farma Especial | Un procedimiento para la preparacion de acicloguanosina. |
| GB8816760D0 (en) * | 1988-07-14 | 1988-08-17 | Wellcome Found | Therapeutic compounds |
| US5994361A (en) * | 1994-06-22 | 1999-11-30 | Biochem Pharma | Substituted purinyl derivatives with immunomodulating activity |
| JP4704223B2 (ja) * | 2006-01-30 | 2011-06-15 | Ｈｏｙａ株式会社 | 送りねじ機構 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5122049A (ja) * | 1974-08-19 | 1976-02-21 | Sanwa Denki Kk | Kahenteikosochi |
-
1977
- 1977-02-28 AU AU22759/77A patent/AU515553B2/en not_active Expired
- 1977-03-01 AR AR266728A patent/AR228232A1/es active
- 1977-03-01 CH CH257177A patent/CH629806A5/de not_active IP Right Cessation
- 1977-03-01 ZA ZA00771220A patent/ZA771220B/xx unknown
- 1977-03-01 BG BG035556A patent/BG27750A3/xx unknown
- 1977-03-01 RO RO7796630A patent/RO76591A/ro unknown
- 1977-03-01 DD DD197619A patent/DD128611A5/xx unknown
- 1977-03-01 GR GR52881A patent/GR66070B/el unknown
- 1977-03-01 BE BE175383A patent/BE851972R/xx not_active IP Right Cessation
- 1977-03-01 CA CA272,888A patent/CA1086316A/en not_active Expired
- 1977-03-01 LU LU76869A patent/LU76869A1/xx unknown
- 1977-03-01 FI FI770655A patent/FI60710C/fi not_active IP Right Cessation
- 1977-03-01 BG BG036534A patent/BG28067A3/xx unknown
- 1977-03-01 SU SU772455681A patent/SU637086A3/ru active
- 1977-03-01 SE SE7702233A patent/SE433216B/xx not_active IP Right Cessation
- 1977-03-01 PL PL1977196356A patent/PL115267B1/pl not_active IP Right Cessation
- 1977-03-01 DE DE19772708827 patent/DE2708827A1/de active Granted
- 1977-03-01 AT AT134877A patent/AT361007B/de not_active IP Right Cessation
- 1977-03-01 DK DK88677A patent/DK147824C/da not_active IP Right Cessation
- 1977-03-01 ES ES456432A patent/ES456432A2/es not_active Expired
- 1977-03-01 NL NL7702175A patent/NL7702175A/xx active Search and Examination
- 1977-03-01 IE IE438/77A patent/IE44708B1/en unknown
- 1977-03-01 PL PL1977211568A patent/PL115242B1/pl unknown
- 1977-03-01 FR FR7705924A patent/FR2342972A2/fr active Granted
- 1977-03-01 JP JP2211377A patent/JPS52106896A/ja active Granted
- 1977-03-01 HU HU77WE550A patent/HU176907B/hu not_active IP Right Cessation
-
1980
- 1980-06-12 IT IT8048953A patent/IT8048953A0/it unknown
-
1981
- 1981-07-24 AR AR286218A patent/AR228281A1/es active
- 1981-07-24 AR AR286219A patent/AR228282A1/es active
- 1981-07-24 AR AR286220A patent/AR228283A1/es active
- 1981-08-31 CH CH558581A patent/CH631176A5/de not_active IP Right Cessation
- 1981-08-31 CH CH558781A patent/CH632758A5/de not_active IP Right Cessation
- 1981-08-31 CH CH558681A patent/CH632757A5/de not_active IP Right Cessation
-
1984
- 1984-03-21 NL NL8400896A patent/NL8400896A/nl not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1062257A (en) | Purine compounds and salts thereof | |
| US4199574A (en) | Methods and compositions for treating viral infections and guanine acyclic nucleosides | |
| US4146715A (en) | 2-amido-9-(2-acyloxyethoxymethyl)hypoxanthines | |
| US4843066A (en) | Novel adenosine derivatives and pharmaceutical composition containing them as an active ingredient | |
| US4267171A (en) | C-5 Substituted cytosine nucleosides | |
| KR0162654B1 (ko) | N-(피롤로[2,3-d]피리미딘-3-일아크릴)-글루타민산 유도체 | |
| US4287188A (en) | Purine derivatives | |
| JPH06293764A (ja) | グアニン誘導体及びその製造方法及びそれを含有する製薬組成物 | |
| CA2094270C (en) | Xanthine derivatives | |
| JPS63297381A (ja) | ９−〔２−（ヒドロキシメチル）シクロアルキルメチル〕グアニン類 | |
| HU200461B (en) | Process for producing new 9-(n-hyudroxyalkoxy)-purine derivatives and pharmaceutical compositions comprising such compounds | |
| CA1086316A (en) | Purine acyclic nucleosides | |
| GB2073752A (en) | 2,6-diaminobularines | |
| US4027025A (en) | 8-Azapurine derivatives | |
| US4921858A (en) | 7-deazaguanines as immunomodulators | |
| US4060616A (en) | Purine derivatives with repeating unit | |
| US5002950A (en) | 7-deazaguanines as immunomodulators | |
| US5648489A (en) | Syntheses of acyclic guanine nucleosides | |
| GB1561380A (en) | Esters of hydroxyalkoxyalkyl purines their preparation and pharmaceutical compositions containing them | |
| JP3072600B2 (ja) | 新規化合物、その製法及びそれを含む医薬組成物 | |
| US5126347A (en) | Isomeric dideoxynuclesides | |
| US5098905A (en) | 7-deazaguanines as immunomodulators | |
| KR100290533B1 (ko) | 항바이러스 활성을 가지는 2-아미노퓨린 | |
| US4996319A (en) | -2-Amino-4,6-dichloro-5-(2-cyanomethyl-2-amino-5(cyanomethyl)-4,6-dichloro pyrimidine | |
| CS199666B2 (cs) | Způsob přípravy 9-substituovaných purinů |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |