PH26927A - 9-(2-phosphonomethoxy) purines - Google Patents

9-(2-phosphonomethoxy) purines Download PDF

Info

Publication number: PH26927A
Authority: PH; Philippines
Prior art keywords: compound; hydroxy; ethoxy; solution; methanol
Prior art date: 1987-11-30

Application number

PH37871A

Other languages

English (en)

Inventor

Michael Raymond Harnden

David Malcolm Duckworth

Original Assignee

Beecham Group Plc

Priority date (The priority date 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 date listed.)

1987-11-30

Filing date

1988-11-29

Publication date

1992-12-02

1987-11-30 Priority claimed from GB878727988A external-priority patent/GB8727988D0/en

1988-05-16 Priority claimed from GB888811575A external-priority patent/GB8811575D0/en

1988-11-29 Application filed by Beecham Group Plc filed Critical Beecham Group Plc

1992-12-02 Publication of PH26927A publication Critical patent/PH26927A/en

Links

150000003212 purines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 113
238000000034 method Methods 0.000 claims abstract description 31
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
239000001257 hydrogen Substances 0.000 claims abstract description 26
-1 hydroxy, amino Chemical group 0.000 claims abstract description 18
150000003839 salts Chemical class 0.000 claims abstract description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 15
150000002431 hydrogen Chemical group 0.000 claims abstract description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
125000000217 alkyl group Chemical group 0.000 claims abstract description 7
230000000840 anti-viral effect Effects 0.000 claims abstract description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 7
125000001309 chloro group Chemical group Cl* 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 20
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 15
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 14
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 11
229930024421 Adenine Natural products 0.000 claims description 9
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 9
229960000643 adenine Drugs 0.000 claims description 9
241000713666 Lentivirus Species 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 3
241001529453 unidentified herpesvirus Species 0.000 claims description 3
TVDFUMDFDCRYNG-UHFFFAOYSA-N 2-propoxy-7H-purin-6-amine Chemical compound C(CC)OC1=NC(=C2NC=NC2=N1)N TVDFUMDFDCRYNG-UHFFFAOYSA-N 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims 2
HRVFEVBDZIXIGY-UHFFFAOYSA-N 2-(6-aminopurin-9-yl)oxyethoxymethylphosphonic acid Chemical compound NC1=NC=NC2=C1N=CN2OCCOCP(O)(O)=O HRVFEVBDZIXIGY-UHFFFAOYSA-N 0.000 claims 1
ZBCJINMBRNZUHY-UHFFFAOYSA-N 2-[(2-amino-6-oxo-3h-purin-9-yl)oxy]ethoxymethylphosphonic acid Chemical compound N1C(N)=NC(=O)C2=C1N(OCCOCP(O)(O)=O)C=N2 ZBCJINMBRNZUHY-UHFFFAOYSA-N 0.000 claims 1
KKGVUSBPIMGXMR-UHFFFAOYSA-N 9-[2-(diethoxyphosphorylmethoxy)ethoxy]purine-2,6-diamine Chemical compound N1=C(N)N=C2N(OCCOCP(=O)(OCC)OCC)C=NC2=C1N KKGVUSBPIMGXMR-UHFFFAOYSA-N 0.000 claims 1
OOUMOJPQKYZQSM-UHFFFAOYSA-N C(CC)ONC=1NC(C=2NC=NC2N1)=O Chemical compound C(CC)ONC=1NC(C=2NC=NC2N1)=O OOUMOJPQKYZQSM-UHFFFAOYSA-N 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 9
238000002360 preparation method Methods 0.000 abstract description 5
239000003814 drug Substances 0.000 abstract description 4
125000001424 substituent group Chemical group 0.000 abstract description 4
125000005042 acyloxymethyl group Chemical group 0.000 abstract description 3
125000005843 halogen group Chemical group 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 185
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 112
239000000243 solution Substances 0.000 description 78
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 38
239000000203 mixture Substances 0.000 description 38
239000002904 solvent Substances 0.000 description 36
239000007787 solid Substances 0.000 description 32
238000005160 1H NMR spectroscopy Methods 0.000 description 31
239000000741 silica gel Substances 0.000 description 31
229910002027 silica gel Inorganic materials 0.000 description 31
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
239000000543 intermediate Substances 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
238000005481 NMR spectroscopy Methods 0.000 description 17
239000000706 filtrate Substances 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
235000019441 ethanol Nutrition 0.000 description 15
238000001816 cooling Methods 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
229910021529 ammonia Inorganic materials 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
241000700605 Viruses Species 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 9
229940035024 thioglycerol Drugs 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
239000012298 atmosphere Substances 0.000 description 8
239000011159 matrix material Substances 0.000 description 8
229920005989 resin Polymers 0.000 description 8
239000011347 resin Substances 0.000 description 8
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 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
IRUNKQSGDBYUDC-UHFFFAOYSA-N diethoxymethyl acetate Chemical compound CCOC(OCC)OC(C)=O IRUNKQSGDBYUDC-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
239000011734 sodium Substances 0.000 description 6
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 5
229920000936 Agarose Polymers 0.000 description 5
101150065749 Churc1 gene Proteins 0.000 description 5
102100038239 Protein Churchill Human genes 0.000 description 5
239000012267 brine Substances 0.000 description 5
244000309466 calf Species 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
239000002253 acid 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
239000013553 cell monolayer Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
239000000499 gel Substances 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
241000700588 Human alphaherpesvirus 1 Species 0.000 description 3
241000701074 Human alphaherpesvirus 2 Species 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
206010035148 Plague Diseases 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
241000607479 Yersinia pestis Species 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
229910002091 carbon monoxide Inorganic materials 0.000 description 3
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
238000012423 maintenance Methods 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 3
INAVTYBULIFSLK-UHFFFAOYSA-N n-(4,6-dichloropyrimidin-5-yl)formamide Chemical compound ClC1=NC=NC(Cl)=C1NC=O INAVTYBULIFSLK-UHFFFAOYSA-N 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
RUEXAUMNROPPKR-UHFFFAOYSA-N 2-(9-phenylmethoxypurin-6-yl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(C=1N=C2)=NC=NC=1N2OCC1=CC=CC=C1 RUEXAUMNROPPKR-UHFFFAOYSA-N 0.000 description 2
CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 2
HKCXKNGHGLCFHK-UHFFFAOYSA-N 2-methoxy-7h-purine Chemical compound COC1=NC=C2NC=NC2=N1 HKCXKNGHGLCFHK-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
FCZOVUJWOBSMSS-UHFFFAOYSA-N 5-[(6-aminopurin-9-yl)methyl]-5-methyl-3-methylideneoxolan-2-one Chemical compound C1=NC2=C(N)N=CN=C2N1CC1(C)CC(=C)C(=O)O1 FCZOVUJWOBSMSS-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
241000700584 Simplexvirus Species 0.000 description 2
229910000831 Steel Inorganic materials 0.000 description 2
241000713325 Visna/maedi virus Species 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
238000003556 assay Methods 0.000 description 2
239000002585 base Substances 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000001589 carboacyl group Chemical group 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 2
239000006071 cream Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
231100000135 cytotoxicity Toxicity 0.000 description 2
230000003013 cytotoxicity Effects 0.000 description 2
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
150000002009 diols Chemical class 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
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235000019253 formic acid Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
230000002458 infectious effect Effects 0.000 description 2
239000002054 inoculum Substances 0.000 description 2
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000011777 magnesium Substances 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
239000000463 material Substances 0.000 description 2
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
SJUZRTBKERGCTK-UHFFFAOYSA-N n-(4,6-dichloro-2-formamidopyrimidin-5-yl)formamide Chemical compound ClC1=NC(NC=O)=NC(Cl)=C1NC=O SJUZRTBKERGCTK-UHFFFAOYSA-N 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000002245 particle Substances 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
235000015497 potassium bicarbonate Nutrition 0.000 description 2
229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
239000011736 potassium bicarbonate Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
238000001179 sorption measurement Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000010959 steel Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
238000005406 washing Methods 0.000 description 2
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
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229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Classifications

- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
- 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
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
- 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

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Virology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Jib Cranes (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Electrically Driven Valve-Operating Means (AREA)
Piezo-Electric Or Mechanical Vibrators, Or Delay Or Filter Circuits (AREA)
Liquid Crystal (AREA)
Superconductors And Manufacturing Methods Therefor (AREA)
Sub-Exchange Stations And Push- Button Telephones (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Steroid Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

PH37871A 1987-11-30 1988-11-29 9-(2-phosphonomethoxy) purines PH26927A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB878727988A GB8727988D0 (en)	1987-11-30	1987-11-30	Novel compounds
GB888811575A GB8811575D0 (en)	1988-05-16	1988-05-16	Novel compounds

Publications (1)

Publication Number	Publication Date
PH26927A true PH26927A (en)	1992-12-02

Family

ID=26293121

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH37871A PH26927A (en)	1987-11-30	1988-11-29	9-(2-phosphonomethoxy) purines

Country Status (20)

Country	Link
EP (1)	EP0319228B1 (da)
JP (1)	JPH02293A (da)
KR (1)	KR890008141A (da)
AT (1)	ATE113601T1 (da)
AU (1)	AU617724B2 (da)
DE (1)	DE3852008T2 (da)
DK (1)	DK663588A (da)
ES (1)	ES2064361T3 (da)
FI (1)	FI885544A (da)
GR (1)	GR3014910T3 (da)
HU (1)	HU202244B (da)
IE (1)	IE883550L (da)
IL (1)	IL88518A (da)
MA (1)	MA21450A1 (da)
MY (1)	MY103502A (da)
NO (1)	NO885313L (da)
NZ (1)	NZ227104A (da)
PH (1)	PH26927A (da)
PL (3)	PL160924B1 (da)
PT (1)	PT89098B (da)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5247085A (en) *	1987-11-30	1993-09-21	Beecham Group P.L.C.	Antiviral purine compounds
EP0353955A3 (en) *	1988-08-02	1991-08-14	Beecham Group Plc	Novel compounds
GB8907173D0 (en) *	1989-03-30	1989-05-10	Beecham Group Plc	Novel compounds
GB8912043D0 (en) *	1989-05-25	1989-07-12	Beecham Group Plc	Novel compounds
EP0405748A1 (en) *	1989-05-30	1991-01-02	Beecham Group p.l.c.	Phosphonoderivative of purine with antiviral activity
US5208221A (en) *	1990-11-29	1993-05-04	Bristol-Myers Squibb Company	Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives
GB9205917D0 (en) *	1992-03-18	1992-04-29	Smithkline Beecham Plc	Pharmaceuticals
EP0719274A1 (en) *	1993-09-17	1996-07-03	Gilead Sciences, Inc.	Method for dosing therapeutic compounds
US5798340A (en)	1993-09-17	1998-08-25	Gilead Sciences, Inc.	Nucleotide analogs
GB9821058D0 (en)	1998-09-28	1998-11-18	Univ Cardiff	Chemical compound

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3646049A (en) *	1970-03-05	1972-02-29	Merck & Co Inc	Acylaminobenzimidazole derivatives
CS263951B1 (en) *	1985-04-25	1989-05-12	Antonin Holy	9-(phosponylmethoxyalkyl)adenines and method of their preparation

1988
- 1988-11-28 EP EP88311252A patent/EP0319228B1/en not_active Expired - Lifetime
- 1988-11-28 AU AU26311/88A patent/AU617724B2/en not_active Ceased
- 1988-11-28 AT AT88311252T patent/ATE113601T1/de not_active IP Right Cessation
- 1988-11-28 IE IE883550A patent/IE883550L/xx unknown
- 1988-11-28 PL PL1988281367A patent/PL160924B1/pl unknown
- 1988-11-28 IL IL8851888A patent/IL88518A/xx unknown
- 1988-11-28 PL PL1988281368A patent/PL160927B1/pl unknown
- 1988-11-28 NZ NZ227104A patent/NZ227104A/en unknown
- 1988-11-28 PT PT89098A patent/PT89098B/pt not_active IP Right Cessation
- 1988-11-28 MY MYPI88001372A patent/MY103502A/en unknown
- 1988-11-28 DK DK663588A patent/DK663588A/da not_active Application Discontinuation
- 1988-11-28 PL PL1988276046A patent/PL158762B1/pl unknown
- 1988-11-28 ES ES88311252T patent/ES2064361T3/es not_active Expired - Lifetime
- 1988-11-28 DE DE3852008T patent/DE3852008T2/de not_active Expired - Fee Related
- 1988-11-28 MA MA21693A patent/MA21450A1/fr unknown
- 1988-11-29 FI FI885544A patent/FI885544A/fi not_active Application Discontinuation
- 1988-11-29 JP JP63299785A patent/JPH02293A/ja active Pending
- 1988-11-29 PH PH37871A patent/PH26927A/en unknown
- 1988-11-29 NO NO88885313A patent/NO885313L/no unknown
- 1988-11-30 KR KR1019880016027A patent/KR890008141A/ko not_active Application Discontinuation
- 1988-11-30 HU HU886112A patent/HU202244B/hu not_active IP Right Cessation
1995
- 1995-02-01 GR GR940404074T patent/GR3014910T3/el unknown

Also Published As

Publication number	Publication date
NZ227104A (en)	1991-11-26
NO885313L (no)	1989-05-31
PT89098B (pt)	1993-03-31
HU202244B (en)	1991-02-28
FI885544A (fi)	1989-05-31
GR3014910T3 (en)	1995-05-31
DK663588A (da)	1989-05-31
EP0319228A2 (en)	1989-06-07
AU2631188A (en)	1989-06-15
DE3852008D1 (de)	1994-12-08
PL281368A1 (en)	1990-05-28
PT89098A (pt)	1988-12-01
DK663588D0 (da)	1988-11-28
JPH02293A (ja)	1990-01-05
FI885544A0 (fi)	1988-11-29
IE883550L (en)	1989-05-30
HUT50352A (en)	1990-01-29
PL160927B1 (pl)	1993-05-31
ATE113601T1 (de)	1994-11-15
DE3852008T2 (de)	1995-03-23
EP0319228B1 (en)	1994-11-02
AU617724B2 (en)	1991-12-05
ES2064361T3 (es)	1995-02-01
NO885313D0 (no)	1988-11-29
MA21450A1 (fr)	1989-07-01
KR890008141A (ko)	1989-07-10
PL281367A1 (en)	1990-05-28
IL88518A (en)	1994-02-27
EP0319228A3 (en)	1990-05-16
PL158762B1 (en)	1992-10-30
PL276046A1 (en)	1990-01-08
IL88518A0 (en)	1989-06-30
MY103502A (en)	1993-06-30
PL160924B1 (en)	1993-05-31

Publication	Publication Date	Title
US5055458A (en)	1991-10-08	Purine derivatives having antiviral activity
CA2479846C (en)	2007-07-24	Phosphonomethoxymethylpurine/pyrimidine derivatives
US6069249A (en)	2000-05-30	Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability
US5792756A (en)	1998-08-11	Prodrugs of phosphonates
EP0343133B1 (en)	1992-04-08	Derivatives of purine, process for their preparation and a pharmaceutical preparation
WO2005090370A1 (en)	2005-09-29	Pharmacologically active agents containing esterified phosphonates and methods for use thereof
JP2012153731A (ja)	2012-08-16	抗ウイルスヌクレオチド類似物としてのホスホネート基を有するピリミジン化合物
EP0502690B1 (en)	1999-12-01	Cyclopropane derivative
PH26927A (en)	1992-12-02	9-(2-phosphonomethoxy) purines
US5247085A (en)	1993-09-21	Antiviral purine compounds
PL150925B1 (en)	1990-07-31	Purine compounds.
US5108994A (en)	1992-04-28	Antiviral purine derivatives
US5565461A (en)	1996-10-15	Derivatives of purine, process for their preparation and a pharmaceutical preparation
US5166198A (en)	1992-11-24	Antiviral phosphonylalkoxy purines
EP0130126A1 (en)	1985-01-02	(S)-9-(2,3-dihydroxy-1-propoxymethyl) guanine and its acyl derivatives, their preparation and their application as antiherpetic agents
AU626300C (en)	1993-02-11	Derivatives of purine, process for their preparation and a pharmaceutical preparation
CA2015671C (en)	2000-04-25	Phosphonomethoxytetrahydrofuranyl-purine/pyrimidine derivatives
NO177306B (no)	1995-05-15	Analogifremgangsmåte for fremstilling av terapautisk aktive purinderivater