CS263951B1 - 9-(phosponylmethoxyalkyl)adenines and method of their preparation - Google Patents

9-(phosponylmethoxyalkyl)adenines and method of their preparation Download PDF

Info

Publication number: CS263951B1
Authority: CS; Czechoslovakia
Prior art keywords: formula; adenine; compound; dimethylformamide; compounds
Prior art date: 1985-04-25

Application number

CS853017A

Other languages

Czech (cs)

English (en)

Inventor

Antonin Holy

Ivan Rosenberg

Original Assignee

Antonin Holy

Ivan Rosenberg

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.)

1985-04-25

Filing date

1985-04-25

Publication date

1989-05-12

1985-04-25 Application filed by Antonin Holy, Ivan Rosenberg filed Critical Antonin Holy

1985-04-25 Priority to CS853017A priority Critical patent/CS263951B1/cs

1986-04-11 Priority to DK198601678A priority patent/DK173625B1/da

1986-04-16 Priority to AT86302822T priority patent/ATE78259T1/de

1986-04-16 Priority to EP86302822A priority patent/EP0206459B1/en

1986-04-16 Priority to DE8686302822T priority patent/DE3686002T2/de

1986-04-17 Priority to AU56328/86A priority patent/AU580151B2/en

1986-04-23 Priority to NZ215925A priority patent/NZ215925A/xx

1986-04-24 Priority to CA000507444A priority patent/CA1295614C/en

1986-04-24 Priority to NO861621A priority patent/NO174510B/no

1986-04-24 Priority to JP61093514A priority patent/JPS61275289A/ja

1986-04-25 Priority to US06/856,299 priority patent/US4808716A/en

1986-04-27 Priority to EG243/86A priority patent/EG18079A/xx

1989-05-12 Publication of CS263951B1 publication Critical patent/CS263951B1/cs

1996-12-05 Priority to HK213296A priority patent/HK213296A/xx

Links

GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 title claims abstract description 25
238000000034 method Methods 0.000 title claims abstract description 15
238000002360 preparation method Methods 0.000 title claims abstract description 11
150000001875 compounds Chemical class 0.000 claims abstract description 33
-1 methylene, ethylene, propylene, ethylidene, methoxyethylene, benzyloxyethylene Chemical group 0.000 claims abstract description 23
UAYCAARGGQRWMQ-UHFFFAOYSA-N 1-ethenoxy-1-ethoxyethane Chemical group CCOC(C)OC=C UAYCAARGGQRWMQ-UHFFFAOYSA-N 0.000 claims abstract description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 47
239000000203 mixture Substances 0.000 claims description 16
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 10
239000012312 sodium hydride Substances 0.000 claims description 9
229910000104 sodium hydride Inorganic materials 0.000 claims description 9
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
229910021529 ammonia Inorganic materials 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
239000000741 silica gel Substances 0.000 claims description 5
229910002027 silica gel Inorganic materials 0.000 claims description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 3
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 claims description 2
150000001340 alkali metals Chemical class 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims description 2
238000004587 chromatography analysis Methods 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
238000004255 ion exchange chromatography Methods 0.000 claims description 2
NGVNAUIRSOXAJB-UHFFFAOYSA-N prop-1-ene-1,2-diol Chemical group CC(O)=CO NGVNAUIRSOXAJB-UHFFFAOYSA-N 0.000 claims description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims 1
NMVZYNYULBGMRI-UHFFFAOYSA-N 1-methoxybuta-1,2-diene Chemical group COC=C=CC NMVZYNYULBGMRI-UHFFFAOYSA-N 0.000 claims 1
IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims 1
239000003456 ion exchange resin Substances 0.000 claims 1
229920003303 ion-exchange polymer Polymers 0.000 claims 1
230000000840 anti-viral effect Effects 0.000 abstract description 3
230000004071 biological effect Effects 0.000 abstract description 3
230000000694 effects Effects 0.000 abstract description 3
125000000217 alkyl group Chemical group 0.000 abstract description 2
125000004432 carbon atom Chemical group C* 0.000 abstract 1
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
229930024421 Adenine Natural products 0.000 description 21
229960000643 adenine Drugs 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
239000000243 solution Substances 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
229910003002 lithium salt Inorganic materials 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
159000000002 lithium salts Chemical class 0.000 description 7
239000000126 substance Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
241000700605 Viruses Species 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000011734 sodium Substances 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
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 3
150000007513 acids Chemical class 0.000 description 3
239000002585 base Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
150000001768 cations Chemical class 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
230000000120 cytopathologic effect Effects 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
229910052698 phosphorus Inorganic materials 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
229960001866 silicon dioxide Drugs 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
BYUNYALHUMSCSA-UHFFFAOYSA-N 2-ethenoxyoxane Chemical group C=COC1CCCCO1 BYUNYALHUMSCSA-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
239000005909 Kieselgur Substances 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
125000003435 aroyl group Chemical group 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
210000004027 cell Anatomy 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
WGQMNJYLZXTHIN-UHFFFAOYSA-N dimethoxyphosphorylmethyl 4-methylbenzenesulfonate Chemical compound COP(=O)(OC)COS(=O)(=O)C1=CC=C(C)C=C1 WGQMNJYLZXTHIN-UHFFFAOYSA-N 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
210000003292 kidney cell Anatomy 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
238000003756 stirring Methods 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 2
238000005406 washing Methods 0.000 description 2
150000000180 1,2-diols Chemical class 0.000 description 1
XVNBPVQOGWKDEA-UHFFFAOYSA-N 3-(6-aminopurin-9-yl)-2-phenylmethoxypropan-1-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1CC(CO)OCC1=CC=CC=C1 XVNBPVQOGWKDEA-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
241000450599 DNA viruses Species 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
TYBWABJIIOVYOR-UHFFFAOYSA-N OCC(C(O)=O)OP(=O)=O Chemical compound OCC(C(O)=O)OP(=O)=O TYBWABJIIOVYOR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
241000700618 Vaccinia virus Species 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
SUPKOOSCJHTBAH-UHFFFAOYSA-N adefovir Chemical compound NC1=NC=NC2=C1N=CN2CCOCP(O)(O)=O SUPKOOSCJHTBAH-UHFFFAOYSA-N 0.000 description 1
150000003838 adenosines Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
229910001863 barium hydroxide Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
230000003559 chemosterilizing effect Effects 0.000 description 1
FZXSSJIKXCFPDP-UHFFFAOYSA-N chloro(dichlorophosphoryl)methane Chemical compound ClCP(Cl)(Cl)=O FZXSSJIKXCFPDP-UHFFFAOYSA-N 0.000 description 1
MOFCYHDQWIZKMY-UHFFFAOYSA-N chloromethylphosphonic acid Chemical compound OP(O)(=O)CCl MOFCYHDQWIZKMY-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000002242 deionisation method Methods 0.000 description 1
150000005690 diesters Chemical class 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
238000007865 diluting Methods 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
AZDCYKCDXXPQIK-UHFFFAOYSA-N ethenoxymethylbenzene Chemical group C=COCC1=CC=CC=C1 AZDCYKCDXXPQIK-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
150000004673 fluoride salts Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
AFQIYTIJXGTIEY-UHFFFAOYSA-N hydrogen carbonate;triethylazanium Chemical compound OC(O)=O.CCN(CC)CC AFQIYTIJXGTIEY-UHFFFAOYSA-N 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Inorganic materials [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 1
238000003760 magnetic stirring Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
DTMFTBZNVFUECB-UHFFFAOYSA-N n-[9-(2-hydroxyethyl)purin-6-yl]benzamide Chemical compound N1=CN=C2N(CCO)C=NC2=C1NC(=O)C1=CC=CC=C1 DTMFTBZNVFUECB-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
230000007505 plaque formation Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
150000005691 triesters Chemical class 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
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 1
241001529453 unidentified herpesvirus Species 0.000 description 1
238000010626 work up procedure Methods 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
- 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

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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)
Molecular Biology (AREA)
Biochemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Virology (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CS853017A 1985-04-25 1985-04-25 9-(phosponylmethoxyalkyl)adenines and method of their preparation CS263951B1 (en)

Priority Applications (13)

Application Number	Priority Date	Filing Date	Title
CS853017A CS263951B1 (en)	1985-04-25	1985-04-25	9-(phosponylmethoxyalkyl)adenines and method of their preparation
DK198601678A DK173625B1 (da)	1985-04-25	1986-04-11	9-(fosfonylmethoxyalkyl)adeniner, fremgangsmåde til fremstilling og anvendelse af samme
AT86302822T ATE78259T1 (de)	1985-04-25	1986-04-16	9-(phosphonylmethoxyalkyl)-adenine, verfahren zu ihrer herstellung und ihre verwendung.
EP86302822A EP0206459B1 (en)	1985-04-25	1986-04-16	9-(phosphonylmethoxyalkyl) adenines, method for their preparation and their use
DE8686302822T DE3686002T2 (de)	1985-04-25	1986-04-16	9-(phosphonylmethoxyalkyl)-adenine, verfahren zu ihrer herstellung und ihre verwendung.
AU56328/86A AU580151B2 (en)	1985-04-25	1986-04-17	9-(phosphonylmethoxyalkyl) adenines, the method of preparation and utilization thereof
NZ215925A NZ215925A (en)	1985-04-25	1986-04-23	9-(phosphonylmethoxyalkyl)adenines
CA000507444A CA1295614C (en)	1985-04-25	1986-04-24	9-(phosphonylmethoxyalkyl)adenines, the method of preparation and utilization thereof
NO861621A NO174510B (no)	1985-04-25	1986-04-24	Anlogifremgangsmaate for fremstilling av terapeutisk aktivt 9-(2- fosfonylmethoxyethyl)-adenin
JP61093514A JPS61275289A (ja)	1985-04-25	1986-04-24	９−（ホスホニルメトキシアルキル）アデニン，その製造法及びその利用
US06/856,299 US4808716A (en)	1985-04-25	1986-04-25	9-(phosponylmethoxyalkyl) adenines, the method of preparation and utilization thereof
EG243/86A EG18079A (en)	1985-04-25	1986-04-27	Process for preparing of 9-(phosphonylmetoxya-lkyl)adenines and utilisation thereof
HK213296A HK213296A (en)	1985-04-25	1996-12-05	9-(phosphonyl-methoxyalkyl) adenines method for their preparation and their use

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CS853017A CS263951B1 (en)	1985-04-25	1985-04-25	9-(phosponylmethoxyalkyl)adenines and method of their preparation

Publications (1)

Publication Number	Publication Date
CS263951B1 true CS263951B1 (en)	1989-05-12

Family

ID=5369028

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS853017A CS263951B1 (en)	1985-04-25	1985-04-25	9-(phosponylmethoxyalkyl)adenines and method of their preparation

Country Status (13)

Country	Link
US (1)	US4808716A (da)
EP (1)	EP0206459B1 (da)
JP (1)	JPS61275289A (da)
AT (1)	ATE78259T1 (da)
AU (1)	AU580151B2 (da)
CA (1)	CA1295614C (da)
CS (1)	CS263951B1 (da)
DE (1)	DE3686002T2 (da)
DK (1)	DK173625B1 (da)
EG (1)	EG18079A (da)
HK (1)	HK213296A (da)
NO (1)	NO174510B (da)
NZ (1)	NZ215925A (da)

Families Citing this family (86)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5047533A (en) *	1983-05-24	1991-09-10	Sri International	Acyclic purine phosphonate nucleotide analogs
US4845084A (en) *	1984-01-26	1989-07-04	Merck & Co., Inc.	Phosphate derivatives of substituted butyl guanines, antiviral compositions containing them, and methods of treating viral infections with them
CS264222B1 (en) *	1986-07-18	1989-06-13	Holy Antonin	N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them
US5650510A (en) *	1986-11-18	1997-07-22	Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic	Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives
NZ222553A (en) *	1986-11-18	1991-07-26	Bristol Myers Co	Phosphonomethoxyalkylene purine and pyrimidine derivatives and pharmaceutical compositions
US5247085A (en) *	1987-11-30	1993-09-21	Beecham Group P.L.C.	Antiviral purine compounds
IE883550L (en) *	1987-11-30	1989-05-30	Salvatore Mario Pandolfo	Novel compounds
EP0339161A1 (en) *	1988-04-01	1989-11-02	Merrell Dow Pharmaceuticals Inc.	Novel fluorophosphonate nucleotide derivatives
EP0335770B1 (en) *	1988-04-01	1997-01-15	Merrell Pharmaceuticals Inc.	Novel fluorophosphonate nucleotide derivatives
US5284837A (en) *	1988-05-06	1994-02-08	Medivir Ab	Derivatives of purine, process for their preparation and a pharmaceutical preparation
EP0353955A3 (en) *	1988-08-02	1991-08-14	Beecham Group Plc	Novel compounds
US5744600A (en) *	1988-11-14	1998-04-28	Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic	Phosphonomethoxy carbocyclic nucleosides and nucleotides
US4966895A (en) *	1989-02-02	1990-10-30	Merck & Co. Inc.	Cyclic monophosphates of purine and pyrimidine acyclonucleosides as anti-retroviral agents
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
GB8912043D0 (en) *	1989-05-25	1989-07-12	Beecham Group Plc	Novel compounds
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
CS387190A3 (en) *	1990-08-06	1992-03-18	Ustav Organicke Chemie A Bioch	(2r)-2-/di(2-propyl)phosphonylmethoxy/-3-p-toluenesulfonyloxy -1- trimethylacetoxypropane and process for preparing thereof
DE69132276T2 (de) *	1990-08-10	2001-03-01	Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic, Prag/Praha	Verfahren zur herstellung von nukleotiden
DK0481214T3 (da) *	1990-09-14	1999-02-22	Acad Of Science Czech Republic	Prolægemidler af phosphonater
US5208221A (en) *	1990-11-29	1993-05-04	Bristol-Myers Squibb Company	Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives
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
US5514798A (en) *	1993-06-02	1996-05-07	Gilead Sciences, Inc.	Method and cyclic carbonates for nucleotide analogues
US5798340A (en)	1993-09-17	1998-08-25	Gilead Sciences, Inc.	Nucleotide analogs
US5656745A (en) *	1993-09-17	1997-08-12	Gilead Sciences, Inc.	Nucleotide analogs
CA2171868A1 (en) *	1993-09-17	1995-03-23	Petr Alexander	Method for dosing therapeutic compounds
DE4408534A1 (de) *	1994-03-14	1995-09-28	Hoechst Ag	Substituierte N-Ethyl-Glycinderivate zur Herstellung von PNA und PNA-/DNA-Hybriden
US6465650B1 (en)	1995-03-13	2002-10-15	Aventis Pharma Deutschland Gmbh	Substituted N-ethylglycine derivatives for preparing PNA and PNA/DNA hybrids
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
US5877166A (en) *	1996-04-29	1999-03-02	Sri International	Enantiomerically pure 2-aminopurine phosphonate nucleotide analogs as antiviral agents
US5733788A (en) *	1996-07-26	1998-03-31	Gilead Sciences, Inc.	PMPA preparation
AU713374B2 (en) *	1996-07-26	1999-12-02	Gilead Sciences, Inc.	Nucleotide analogs
ES2236389T3 (es) *	1997-07-25	2005-07-16	Gilead Sciences, Inc.	Composicion de analogos de nucleotidos y procedimiento de sintesis.
US5935946A (en) *	1997-07-25	1999-08-10	Gilead Sciences, Inc.	Nucleotide analog composition and synthesis method
WO2000029414A1 (fr) *	1998-11-18	2000-05-25	Viktor Veniaminovich Tets	Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates
US7205404B1 (en) *	1999-03-05	2007-04-17	Metabasis Therapeutics, Inc.	Phosphorus-containing prodrugs
KR100767432B1 (ko)	2000-07-21	2007-10-17	길리애드 사이언시즈, 인코포레이티드	포스포네이트 뉴클레오티드 유사체의 전구 약물과 그것의 선택 및 제조 방법
CZ297267B6 (cs) *	2001-06-29	2006-10-11	Ústav organické chemie a biochemie AV CR	Deriváty pyrimidinu nesoucí fosfonátovou skupinu,zpusob jejich prípravy, jejich pouzití pro lécbu a farmaceutické prípravky tyto látky obsahující
KR20040054775A (ko) *	2001-11-14	2004-06-25	바이오크리스트 파마수티컬즈, 인코퍼레이티드	뉴클레오시드, 그들의 조합약과 알앤에이 바이러스성폴리머라제의 억제제로서의 사용방법
US7388002B2 (en)	2001-11-14	2008-06-17	Biocryst Pharmaceuticals, Inc.	Nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases
JP4476811B2 (ja)	2002-05-13	2010-06-09	メタバシス・セラピューティクス・インコーポレイテッド	Ｐｍｅａおよびそのアナログの新規ホスホン酸系プロドラッグ
WO2003095665A2 (en)	2002-05-13	2003-11-20	Metabasis Therapeutics, Inc.	Pmea and pmpa cyclic producing synthesis
AU2003284800A1 (en) *	2002-11-12	2004-06-03	Tianjin Kinsly Pharmaceutical Co., Ltd.	A new crystal form of adefovir dipivoxil and its composition
US20060246130A1 (en)	2003-01-14	2006-11-02	Dahl Terrence C	Compositions and methods for combination antiviral therapy
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
NZ544988A (en) *	2003-07-30	2009-11-27	Gilead Sciences Inc	Nucleobase phosphonate analogs for antiviral treatment
CN103374041B (zh) *	2004-06-08	2017-05-10	症变治疗公司	路易斯酸介导的环状酯的合成
CN100338080C (zh) *	2004-06-16	2007-09-19	山东中科泰斗化学有限公司	9－[2－(膦羧基甲氧基)乙基]腺嘌呤双环醇酯及其制备方法
UA93354C2 (ru)	2004-07-09	2011-02-10	Гилиад Сайенсиз, Инк.	Местный противовирусный препарат
ES2401285T3 (es)	2004-12-16	2013-04-18	The Regents Of The University Of California	Fármacos con el pulmón como diana
US20090156545A1 (en) *	2005-04-01	2009-06-18	Hostetler Karl Y	Substituted Phosphate Esters of Nucleoside Phosphonates
TWI471145B (zh)	2005-06-13	2015-02-01	Bristol Myers Squibb & Gilead Sciences Llc	單一式藥學劑量型
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
US20090148407A1 (en)	2005-07-25	2009-06-11	Intermune, Inc.	Novel Macrocyclic Inhibitors of Hepatitis C Virus Replication
EP1907391A1 (en) *	2005-07-26	2008-04-09	Hetero Drugs Limited	Novel process for acyclic phosphonate nucleotide analogs
CN101415705B (zh) *	2005-10-11	2011-10-26	因特蒙公司	抑制丙型肝炎病毒复制的化合物和方法
AU2006325404B2 (en) *	2005-12-14	2012-03-01	Cipla Limited	Pharmaceutical combination comprising nucleotide and nucleoside reverse transcriptase inhibitors (such as tenofovir and lamivudine) in different parts of the dosage unit
FR2908133B1 (fr) *	2006-11-08	2012-12-14	Centre Nat Rech Scient	Nouveaux analogues de nucleotides comme molecules precurseurs d'antiviraux
PT2514750E (pt)	2007-06-18	2014-01-23	Sunshine Lake Pharma Co Ltd	Tiazolil dihidropirimidinas substituídas com bromo-fenilo
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
WO2009120358A1 (en) *	2008-03-27	2009-10-01	Nektar Therapeutics	Oligomer-nitrogenous base conjugates
US7935817B2 (en) *	2008-03-31	2011-05-03	Apotex Pharmachem Inc.	Salt form and cocrystals of adefovir dipivoxil and processes for preparation thereof
CN102046622A (zh) *	2008-04-15	2011-05-04	因特蒙公司	丙型肝炎病毒复制的新颖大环抑制剂
US8173621B2 (en)	2008-06-11	2012-05-08	Gilead Pharmasset Llc	Nucleoside cyclicphosphates
TW201010692A (en)	2008-06-19	2010-03-16	Public Univ Corp Nagoya City Univ	Pharmaceutical composition for treatment or prevention of hbv infection
JP2012505897A (ja) *	2008-10-15	2012-03-08	インターミューン・インコーポレーテッド	治療用抗ウイルス性ペプチド
SG194404A1 (en)	2008-12-23	2013-11-29	Gilead Pharmasset Llc	Synthesis of purine nucleosides
AU2009329917B2 (en)	2008-12-23	2016-03-31	Gilead Pharmasset Llc	Nucleoside analogs
AR074897A1 (es)	2008-12-23	2011-02-23	Pharmasset Inc	Fosforamidatos de nucleosidos
TR201109333T1 (tr)	2009-03-26	2012-01-23	Daewoong Pharmaceutical Co. Ltd.	Adefovir dipivoksilin yeni kristal formları ve bunların hazırlama işlemleri.
PH12012500602A1 (en) *	2009-09-28	2017-08-23	Intermune Inc	Cyclic peptide inhibitors of hepatitis c virus replication
WO2011041551A1 (en) *	2009-10-01	2011-04-07	Intermune, Inc.	Therapeutic antiviral peptides
PT2609923T (pt)	2010-03-31	2017-08-30	Gilead Pharmasset Llc	Processo para a cristalização de 2-(((s)- (perfluorofenoxi)(fenoxi)fosforil)amino)propanoato de (s)-isopropilo
CN104203275A (zh)	2010-06-09	2014-12-10	疫苗技术股份有限公司	用于增强抗逆转录病毒治疗的hiv感染者的治疗性免疫
ES2551738T3 (es)	2010-06-11	2015-11-23	Gilead Sciences, Inc.	Formulaciones tópicas antivirales para la prevención de la transmisión del VHS-2
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.
WO2012154698A2 (en) *	2011-05-06	2012-11-15	Mckenna Charles E	Method to improve antiviral activity of nucleotide analogue drugs
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US9227990B2 (en)	2012-10-29	2016-01-05	Cipla Limited	Antiviral phosphonate analogues and process for preparation thereof
WO2014143643A1 (en)	2013-03-15	2014-09-18	The Regents Of The University Of California, A California Corporation	Acyclic nucleoside phosphonate diesters
CN106061984A (zh)	2014-02-13	2016-10-26	配体药物公司	前药化合物及其用途
US10167302B2 (en) *	2014-05-23	2019-01-01	University College Cork	Phosphonate nucleosides useful in the treatment of viral diseases
EP3164136A4 (en)	2014-07-02	2018-04-04	Ligand Pharmaceuticals, Inc.	Prodrug compounds and uses therof
AU2015317972B2 (en)	2014-09-15	2019-10-17	The Regents Of The University Of California	Nucleotide analogs
WO2017048956A1 (en)	2015-09-15	2017-03-23	The Regents Of The University Of California	Nucleotide analogs
EP3372227A1 (en)	2017-03-06	2018-09-12	MH10 Spolka z ograniczona odpowiedzialnoscia	Tablet formulation of adefovir dipivoxil
JP2021509907A (ja)	2018-01-09	2021-04-08	リガンド・ファーマシューティカルズ・インコーポレイテッド	アセタール化合物およびその治療的使用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1523865A (en) *	1974-09-02	1978-09-06	Wellcome Found	Purine compunds and salts thereof
US4347360A (en) *	1980-09-16	1982-08-31	Ens Bio Logicals Inc.	Ring open nucleoside analogues
CS233665B1 (en) *	1983-01-06	1985-03-14	Antonin Holy	Processing of isomere o-phosphonylmethylderivative of anantiomere racemic vicinal diene
AU8092587A (en) *	1986-11-18	1988-05-19	Bristol-Myers Squibb Company	Synthesis of purin-9-ylalkylenoxymethyl phosphonic acids

1985
- 1985-04-25 CS CS853017A patent/CS263951B1/cs not_active IP Right Cessation
1986
- 1986-04-11 DK DK198601678A patent/DK173625B1/da not_active IP Right Cessation
- 1986-04-16 DE DE8686302822T patent/DE3686002T2/de not_active Expired - Lifetime
- 1986-04-16 EP EP86302822A patent/EP0206459B1/en not_active Expired - Lifetime
- 1986-04-16 AT AT86302822T patent/ATE78259T1/de not_active IP Right Cessation
- 1986-04-17 AU AU56328/86A patent/AU580151B2/en not_active Expired
- 1986-04-23 NZ NZ215925A patent/NZ215925A/xx unknown
- 1986-04-24 NO NO861621A patent/NO174510B/no unknown
- 1986-04-24 JP JP61093514A patent/JPS61275289A/ja active Granted
- 1986-04-24 CA CA000507444A patent/CA1295614C/en not_active Expired - Lifetime
- 1986-04-25 US US06/856,299 patent/US4808716A/en not_active Expired - Lifetime
- 1986-04-27 EG EG243/86A patent/EG18079A/xx active
1996
- 1996-12-05 HK HK213296A patent/HK213296A/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
JPH0433798B2 (da)	1992-06-04
CA1295614C (en)	1992-02-11
DE3686002T2 (de)	1992-12-17
DE3686002D1 (de)	1992-08-20
DK167886A (da)	1986-10-26
DK167886D0 (da)	1986-04-11
NO861621L (no)	1986-10-27
DK173625B1 (da)	2001-05-07
HK213296A (en)	1996-12-06
AU580151B2 (en)	1989-01-05
NO174510C (da)	1994-05-18
EG18079A (en)	1992-06-30
AU5632886A (en)	1986-10-30
EP0206459B1 (en)	1992-07-15
US4808716A (en)	1989-02-28
JPS61275289A (ja)	1986-12-05
EP0206459A2 (en)	1986-12-30
EP0206459A3 (en)	1987-05-20
ATE78259T1 (de)	1992-08-15
NZ215925A (en)	1989-01-27
NO174510B (no)	1994-02-07

Publication	Publication Date	Title
CS263951B1 (en)	1989-05-12	9-(phosponylmethoxyalkyl)adenines and method of their preparation
JPH0822866B2 (ja)	1996-03-06	プリンおよびピリミジン塩基のｎ−ホスホニルメトキシアルキル誘導体
Wagner et al.	1974	Preparation and synthetic utility of some organotin derivatives of nucleosides
Weimann et al.	1962	Studies on Polynucleotides. XVII. 1 On the Mechanism of Internucleotide Bond Synthesis by the Carbodiimide Method 2
EP0074306B1 (en)	1988-06-01	Anti-viral guanine derivatives
CS233665B1 (en)	1985-03-14	Processing of isomere o-phosphonylmethylderivative of anantiomere racemic vicinal diene
Brown et al.	1952	511. Nucleotides. Part XII. The preparation of cyclic 2′: 3′-phosphates of adenosine, cytidine, and uridine
US5733896A (en)	1998-03-31	N-(3-fluoro-2-phosphonylmethoxypropyl) derivatives of purine and pyrimidine heterocyclic bases, their preparation and use
Hall et al.	1955	Nucleoside Polyphosphates. III. 1 Syntheses of Pyrimidine Nucleoside-2'(3'), 5'-diphosphates
Rosenberg et al.	1988	Phosphonylmethoxyalkyl and phosphonylalkyl derivatives of adenine
Holý et al.	1987	Synthesis of isomeric and enantiomeric O-phosphonylmethyl derivatives of 9-(2, 3-dihydroxypropyl) adenine
Jindřich et al.	1993	Synthesis of N-(3-fluoro-2-phosphonomethoxypropyl)(FPMP) derivatives of heterocyclic bases
Parikh et al.	1957	Analogs of Nucleotides. II. Phosphonate Esters of Ribose and Glucopyranosyl Purine Derivatives1
Tener et al.	1955	Cyclic Phosphates. II. Further Studies of Ribonucleoside 2': 3'-Cyclic Phosphates1
Liboska et al.	1996	Carbocyclic phosphonate-based nucleotide analogs related to PMEA. I. Racemic trans-configured derivatives
EP0540707B1 (en)	1995-11-15	Di(2-PROPYL)ESTERS OF 1-FLUORO-2-PHOSPHONOMETHOXY-3-P-TOLUENESULFONYLOXYPROPANES, THEIR PRODUCING AND UTILIZATION
Alexander et al.	1994	Preparation of 9-(2-phosphonomethoxyethyl) adenine esters as potential prodrugs
Dvořáková et al.	1993	Synthesis and biological effects of N-(2-phosphonomethoxyethyl) derivatives of deazapurine bases
Endová et al.	1998	2′, 3′-O-Phosphonoalkylidene derivatives of ribonucleosides: Synthesis and reactivity
Holý	1989	Synthesis of 3-amino-and 3-azidoanalogs of 9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA)
Ogilvie et al.	1979	Fluoride ion catalyzed alkylation of purines, pyrimidines, nucleosides and nucleotides using alkyl halides
US2815342A (en)	1957-12-03	Synthesis of pyrimidine nucleoside phosphates
US3118876A (en)	1964-01-21	Process for preparing glycoside phosphates
DK149026B (da)	1985-12-23	Analogifremgangsmaade til fremstilling af adeninnucleosidderivater
Alexander et al.	1994	Synthesis of 9-(2-phosphinomethoxyethyl) adenine and related compounds

Legal Events

Date	Code	Title	Description
2000-06-14	MK4A	Patent expired	Effective date: 20000425